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• Brusletto, Berit; Haug, Kari Bente Foss; Olsen, Iselin Sandnes; Kaarbø, Mari; Olstad, Ole Kristoffer & Aspelin, Trude [Vis alle 9 forfattere av denne artikkelen] (2026). RNA profiles in extracellular vesicles from severe sepsis and meningitis patients reveal pathogen-specific immune signatures in meningococcal versus pneumococcal infections. Frontiers in Cellular and Infection Microbiology. 16, s. 1730302–1730302. doi: 10.3389/fcimb.2026.1730302. Fulltekst i vitenarkiv
• Brusletto, Berit; Hellerud, Bernt C; Øvstebø, Reidun & Brandtzæg, Petter (2023). Neisseria meningitidis accumulate in large organs during meningococcal sepsis. Frontiers in Cellular and Infection Microbiology. 13, s. 1–10. doi: 10.3389/fcimb.2023.1298360. Fulltekst i vitenarkiv Vis sammendrag

  Background Neisseria meningitidis (Nm) is the cause of epidemic meningitis and fulminant meningococcal septicemia. The clinical presentations and outcome of meningococcal septic shock is closely related to the circulating levels of lipopolysaccharides (LPS) and of Neisseria meningitidis DNA (Nm DNA). We have previously explored the distribution of Nm DNA in tissues from large organs of patients dying of meningococcal septic shock and in a porcine meningococcal septic shock model. Objective 1) To explore the feasibility of measuring LPS levels in tissues from the large organs in patients with meningococcal septic shock and in a porcine meningococcal septic shock model. 2) To evaluate the extent of contamination of non-specific LPS during the preparation of tissue samples. Patients and methods Plasma, serum, and fresh frozen (FF) tissue samples from the large organs of three patients with lethal meningococcal septic shock and two patients with lethal pneumococcal disease. Samples from a porcine meningococcal septic shock model were included. Frozen tissue samples were thawed, homogenized, and prepared for quantification of LPS by Pyrochrome ® Limulus Amoebocyte Lysate (LAL) assay. Results N. meningitidis DNA and LPS was detected in FF tissue samples from large organs in all patients with meningococcal septic shock. The lungs are the organs with the highest LPS and Nm DNA concentration followed by the heart in two of the three meningococcal shock patients. Nm DNA was not detected in any plasma or tissue sample from patients with lethal pneumococcal infection. LPS was detected at a low level in all FF tissues from the two patients with lethal pneumococcal disease. The experimental porcine meningococcal septic shock model indicates that also in porcinis the highest LPS and Nm DNA concentration are detected in lungs tissue samples. The quantification analysis showed that the highest concentration of both Nm DNA and LPS are in the organs and not in the circulation of patients with lethal meningococcal septic shock. This was also shown in the experimental porcine meningococcal septic shock model. Conclusion Our results suggest that LPS can be quantified in mammalian tissues by using the LAL assay.

• Brusletto, Berit Sletbakk; Hellerud, Bernt C; Olstad, Ole Kristoffer; Øvstebø, Reidun & Brandtzæg, Petter (2022). Transcriptomic changes in the large organs in lethal meningococcal shock are reflected in a porcine shock model. Frontiers in Cellular and Infection Microbiology. 12, s. 1–19. doi: 10.3389/fcimb.2022.908204. Fulltekst i vitenarkiv Vis sammendrag

  Background: Fulminant meningococcal sepsis with shock and multiple organ failure is associated with a massive systemic inflammatory response involving solid organs. We have previously established a porcine model of the disease to study pathophysiologic and possible therapeutic strategies. Objective: This study examined whether the organ specific gene expression profile in such a large animal model reflects the profile seen in patients with fulminant meningococcal sepsis. Patients and methods: Data from gene expression profiles induced in organs from patients (n=5) and the porcine model (n=8) were imported into the Ingenuity pathway analysis (IPA) software for comparison analysis. The number of meningococci in the organs were quantified by real time-PCR. Results: The all-over transcriptional activation between different organs revealed a striking concordance between the patients and the pigs regarding the pattern of transcriptional activation and activated pathways. Comparison analysis demonstrated similar pattern of upregulation of genes being associated with a large range of inflammatory biofunctions in the patients and the porcine model. Genes associated with biofunctions such as organismal death, morbidity and mortality were similarly downregulated in the patients and the porcine model. Comparison analysis of main predicted canonical pathways also demonstrated a high degree of similarity regarding up- and downregulation in both groups. Core analysis revealed different top-upstream regulators in the different organs in the patients. In the patients pro-inflammatory regulators were most activated in the lungs. In the other organs up-stream factors that regulate signaling pathways involved in development, growth, repair and homeostasis and triglyceride synthesis were most activated. In the porcine model, the top-upstream regulators were pro-inflammatory in all organs. The difference may reflect the shorter duration of the porcine experiment than the duration of the patient’s infection before death. Conclusion: The inflammatory responses measured on the transcriptomic level in organs in patients with fulminant meningococcal sepsis is reproduced in the porcine model of the disease, although some differences may exist regarding the top-upregulated factors in individual organs. Thus, this large animal model reproduces important immunological features of meningococcal sepsis and can be a valuable tool in further investigations of inflammatory aspects and possible treatment options.

• Brusletto, Berit Sletbakk; Løberg, Else Marit; Hellerud, Bernt C; Goverud, Ingeborg Løstegaard; Berg, Jens Petter & Olstad, Ole Kristoffer [Vis alle 9 forfattere av denne artikkelen] (2020). Extensive changes in transcriptomic “fingerprints” and immunological cells in the large organs of patients dying of acute septic shock and multiple organ failure caused by Neisseria meningitidis. Frontiers in Cellular and Infection Microbiology. 10:42, s. 1–30. doi: 10.3389/fcimb.2020.00042. Fulltekst i vitenarkiv Vis sammendrag

  Background: Patients developing meningococcal septic shock reveal levels of Neisseria meningitidis (106-108/mL) and endotoxin (101-103 EU/mL) in the circulation and organs, leading to acute cardiovascular, pulmonary and renal failure, coagulopathy and a high case fatality rate within 24 h. Objective: To investigate transcriptional profiles in heart, lungs, kidneys, liver, and spleen and immunostain key inflammatory cells and proteins in post mortem formalin-fixed, paraffin-embedded (FFPE) tissue samples from meningococcal septic shock patients. Patients and Methods: Total RNA was isolated from FFPE and fresh frozen (FF) tissue samples from five patients and two controls (acute non-infectious death). Differential expression of genes was detected using Affymetrix microarray analysis. Lung and heart tissue samples were immunostained for T-and B cells, macrophages, neutrophils and the inflammatory markers PAI-1 and MCP-1. Inflammatory mediators were quantified in lysates from FF tissues. Results: The transcriptional profiles showed a complex pattern of protein-coding and non-coding RNAs with significant regulation of pathways associated with organismal death, cell death and survival, leukocyte migration, cellular movement, proliferation of cells, cell-to-cell signaling, immune cell trafficking, and inflammatory responses in an organ-specific clustering manner. The canonical pathways including acute phase response-, EIF2-, TREM1-, IL-6-, HMBG1-, PPAR signaling, and LXR/RXR activation were associated with acute heart, pulmonary, and renal failure. Fewer genes were regulated in the liver and particularly in the spleen. The main upstream regulators were TNF, IL-1β, IL-6, RICTOR, miR-6739-3p, and CD3. Increased numbers of inflammatory cells (CD68+, MPO+, CD3+, and CD20+) were found in lungs and heart. PAI-1 inhibiting fibrinolysis and MCP-1 attracting leukocyte were found significantly present in the septic tissue samples compared to the controls. Conclusions: FFPE tissue samples can be suitable for gene expression studies as well as immunostaining of specific cells or molecules. The most pronounced gene expression patterns were found in the organs with highest levels of Neisseria meningitidis DNA. Thousands of protein-coding and non-coding RNA transcripts were altered in lungs, heart and kidneys. We identified specific biomarker panels both protein-coding and non-coding RNA transcripts, which differed from organ to organ. Involvement of many genes and pathways add up and the combined effect induce organ failure.

• Mihret, Wude; Brusletto, Berit Sletbakk; Øvstebø, Reidun; Siebke, Anne-Marie; Norheim, Gunnstein & Merid, Yared [Vis alle 15 forfattere av denne artikkelen] (2019). Molecular studies of meningococcal and pneumococcal meningitis patients in Ethiopia. Innate Immunity. ISSN 1753-4259. 25(3), s. 158–167. doi: 10.1177/1753425918806363. Fulltekst i vitenarkiv Vis sammendrag

  Neisseria meningitidis infections in sub-Saharan Africa usually present with distinct symptoms of meningitis but very rarely as fulminant septicemia when reaching hospitals. In Europe, development of persistent meningococcal shock and multiple organ failure occurs in up to 30% of patients and is associated with a bacterial load of >106/ml plasma or serum. We have prospectively studied 27 Ethiopian patients with meningococcal infection as diagnosed and quantified with real-time PCR in the cerebrospinal fluid (CSF) and serum. All presented with symptoms of meningitis and none with fulminant septicemia. The median N. meningitidis copy number (NmDNA) in serum was < 3.5 × 103/ml, never exceeded 1.8 × 105/ml, and was always 10–1000 times higher in CSF than in serum. The levels of LPS in CSF as determined by the limulus amebocyte lysate assay were positively correlated to NmDNA copy number (r = 0.45, P = 0.030), levels of IL-1 receptor antagonist, (r = 0.46, P = 0.017), and matrix metallopeptidase-9 (MMP-9; r = 0.009). We also compared the inflammatory profiles of 19 mediators in CSF of the 26 meningococcal patients (2 died and 2 had immediate severe sequelae) with 16 patients with Streptococcus pneumoniae meningitis (3 died and 3 with immediate severe sequelae). Of 19 inflammatory mediators tested, 9 were significantly higher in patients with pneumococcal meningitis and possibly linked to worse outcome.

• Gopinathan, Unni; Redalen, Kathrine; Siebke, Anne-Marie; Kierulf, Peter; Brandtzæg, Petter & Ree, Anne Hansen [Vis alle 8 forfattere av denne artikkelen] (2018). Large-scale reduction of tyrosine kinase activities in human monocytes stimulated in vitro with N. meningitidis. PLOS ONE. 13(1). doi: 10.1371/journal.pone.0181912. Fulltekst i vitenarkiv Vis sammendrag

  N. meningitidis induces extensive gene expression changes in human monocytes, suggesting that complex networks of signaling pathways are activated during meningococcal sepsis. These effects are modulated by the anti-inflammatory cytokine interleukin-10 (IL-10). To further study changes in signal transduction suggested by mRNA data, we used kinase substrate arrays to identify composite kinase activities induced by lysates from a primary human monocyte model system. Cell lysates were prepared from monocytes treated with the following experimental conditions: 106 N. meningitidis/mL, 25 ng/mL IL-10, 106 N. meningitidis/mL in combination with 25 ng/mL IL-10, and vehicle. Lysates were subjected to kinase activity profiling with Tyrosine Kinase PamChip® arrays containing 144 kinase peptide substrates. In our experimental model, we were not able to detect a statistically significant large-scale change in ex vivo array peptide phosphorylation by lysates from monocytes treated for 15 minutes. Targets of the IL-10 anti-inflammatory response were not identified. A profound inhibition of array peptide phosphorylation by monocytes treated for 60 minutes was identified, suggesting low activity of a large number of kinases associated with different signaling pathways and immune cell functions, including STAT3 activity, Nf-κB and VEGF signaling, and PTEN signaling activity. The peptide representing ZBTB16, which was reduced in phosphorylation by lysates from all three experimental conditions, was in Ingenuity Pathway Analysis identified to be linked to reduced cytokine release and mRNA levels of tumor necrosis factor (TNF), IL-6, and CXCL10. Further studies should investigate changes in tyrosine kinase-mediated signal transduction in human immune cells, in order to evaluate the potential clinical application of kinome profiling in the study of systemic inflammatory responses to pathogens.

• Aass, Hans Christian Dalsbotten; Hellum, Marit Synnøve; Siebke, Anne-Marie; Brandtzæg, Petter; Berg, Jens Petter & Øvstebø, Reidun [Vis alle 7 forfattere av denne artikkelen] (2018). Whole-blood incubation with the Neisseria meningitidis lpxL1 mutant induces less pro-inflammatory cytokines than the wild type, and IL-10 reduces the MyD88-dependent cytokines. Innate Immunity. ISSN 1753-4259. 24(2), s. 101–111. doi: 10.1177/1753425917749299. Fulltekst i vitenarkiv Vis sammendrag

  Levels of bacterial LPS, pro-inflammatory cytokines and IL-10 are related to the severity of meningococcal septicaemia. Patients infected with a Neisseria meninigitidis lpxL1 mutant (Nm-mutant) with penta-acylated lipid A present with a milder meningococcal disease than those infected with hexa-acylated Nm wild type (Nm-wt). The aim was to compare the pro-inflammatory responses after ex vivo incubation with the heat-inactivated Nm-wt or the Nm-mutant in citrated whole blood, and the modulating effects of IL-10. Concomitantly, we measured intracellular IL-6, IL-8 and TNF-α to elucidate which cell types were responsible for the pro-inflammatory responses. Incubation with Nm-wt (106/ml;107/ml;108/ml) resulted in a dose-dependent increase of the MyD88-dependent pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α), which were mainly derived from monocytes. In comparison, only 108/ml of the Nm-mutant significantly increased the concentration of these cytokines. The MyD88-independent cytokines (IP-10, RANTES) were evidently increased after incubation with the Nm-wt but were unaffected by the Nm-mutant. Co-incubation with IL-10 significantly reduced the concentrations of the MyD88-dependent cytokines induced by both the Nm-wt and the Nm-mutant, whereas the MyD88-independent cytokines were almost unaffected. In summary, the Nm-mutant is a weaker inducer of the MyD88-dependent/independent cytokines than the Nm-wt in whole blood, and IL-10 attenuates the Nm-stimulated increase in MyD88-dependent pro-inflammatory cytokines.

• Hellum, Marit Synnøve; Siebke, Anne-Marie; Berg, Jens Petter; Brandtzæg, Petter; Øvstebø, Reidun & Henriksson, Carola (2017). The Neisseria meningitidis lpxL1 mutant induces less tissue factor expression and activity in primary human monocytes and monocyte-derived microvesicles than the wild type meningococcus. Innate Immunity. ISSN 1753-4259. 23(2), s. 196–205. doi: 10.1177/1753425916684201. Fulltekst i vitenarkiv
• Knudsen, Per Kristian; Brandtzæg, Petter; Høiby, Ernst Arne; Bohlin, Jon; Samuelsen, Ørjan & Steinbakk, Martin [Vis alle 9 forfattere av denne artikkelen] (2017). Impact of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in children in a low resistance prevalence setting. PLOS ONE. 12(11). doi: 10.1371/journal.pone.0187618. Fulltekst i vitenarkiv Vis sammendrag

  We prospectively studied the consequences of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in a cohort of children with cystic fibrosis (CF) and a cohort of children with cancer compared to healthy children with no or low antibiotic exposure. The study was conducted in Norway in a low resistance prevalence setting. Sixty longitudinally collected faecal samples from children with CF (n = 32), 88 samples from children with cancer (n = 45) and 127 samples from healthy children (n = 70) were examined. A direct MIC-gradient strip method was used to detect resistant Enterobacteriaceae by applying Etest strips directly onto agar-plates swabbed with faecal samples. Whole genome sequencing (WGS) data were analysed to identify resistance mechanisms in 28 multidrug-resistant Escherichia coli isolates. The prevalence of resistance to third-generation cephalosporins, gentamicin and ciprofloxacin was low in all the study groups. At inclusion the prevalence of ampicillin-resistant E. coli and trimethoprim-sulfamethoxazole-resistant E. coli in the CF group compared to healthy controls was 58.6% vs. 28.4% (p = 0.005) and 48.3% vs. 14.9% (p = 0.001), respectively, with a similar prevalence at the end of the study. The prevalence of resistant enterobacteria was not significantly different in the children with cancer compared to the healthy children, not even at the end of the study when the children with cancer had been treated with repeated courses of broad-spectrum antibiotics. Children with cancer were mainly treated with intravenous antibiotics, while the CF group mainly received peroral treatment. Our observations indicate that the mode of administration of antibiotics and the general level of antimicrobial resistance in the community may have an impact on emergence of resistance in intestinal enterobacteria during antibiotic treatment. The WGS analyses detected acquired resistance genes and/or chromosomal mutations that explained the observed phenotypic resistance in all 28 multidrug-resistant E. coli isolates examined.

• Hellerud, Bernt C; Orrem, Hilde Lang; Dybwik, Knut Gustav; Pischke, Søren Erik; Barratt-Due, Andreas & Castellheim, Albert [Vis alle 15 forfattere av denne artikkelen] (2017). Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis. Journal of Intensive Care. ISSN 2052-0492. 5:21, s. 1–9. doi: 10.1186/s40560-017-0217-0. Fulltekst i vitenarkiv Vis sammendrag

  Background Fulminant meningococcal sepsis, characterized by overwhelming innate immune activation, mostly affects young people and causes high mortality. This study aimed to investigate the effect of targeting two key molecules of innate immunity, complement component C5, and co-receptor CD14 in the Toll-like receptor system, on the inflammatory response in meningococcal sepsis. Methods Meningococcal sepsis was simulated by continuous intravenous infusion of an escalating dose of heat-inactivated Neisseria meningitidis administered over 3 h. The piglets were randomized, blinded to the investigators, to a positive control group (n = 12) receiving saline and to an interventional group (n = 12) receiving a recombinant anti-CD14 monoclonal antibody together with the C5 inhibitor coversin. Results A substantial increase in plasma complement activation in the untreated group was completely abolished in the treatment group (p = 0.006). The following inflammatory mediators were substantially reduced in plasma in the treatment group: Interferon-γ by 75% (p = 0.0001), tumor necrosis factor by 50% (p = 0.01), Interleukin (IL)-8 by 50% (p = 0.03), IL-10 by 40% (p = 0.04), IL-12p40 by 50% (p = 0.03), and granulocyte CD11b (CR3) expression by 20% (p = 0.01). Conclusion Inhibition of C5 and CD14 may be beneficial in attenuating the detrimental effects of complement activation and modulating the cytokine storm in patients with fulminant meningococcal sepsis.

• Gopinathan, Unni; Øvstebø, Reidun; Brusletto, Berit Sletbakk; Olstad, Ole Kristoffer; Kierulf, Peter & Brandtzæg, Petter [Vis alle 7 forfattere av denne artikkelen] (2017). Transcriptomic data from two primary cell models stimulating human monocytes suggest inhibition of oxidative phosphorylation and mitochondrial function by N. meningitidis which is partially up-regulated by IL-10. BMC Immunology. 18:46, s. 1–17. doi: 10.1186/s12865-017-0229-5. Fulltekst i vitenarkiv Vis sammendrag

  Background Biological interpretation of DNA microarray data may differ depending on underlying assumptions and statistical tests of bioinformatics tools used. We used Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) to analyze previously generated DNA microarray data from human monocytes stimulated with N. meningitidis and IL-10 (“the model system”), and with meningococcal sepsis plasma before and after immunodepletion of IL-10 (“the patient plasma system”). The objectives were to compare if the two bioinformatics methods resulted in similar biological interpretation of the datasets, and to identify whether GSEA provided additional insight compared with IPA about the monocyte host response to meningococcal activation. Results In both experimental models, GSEA and IPA identified genes associated with pro-inflammatory innate immune activation, including TNF-signaling, Toll-like receptor signaling, JAK-STAT-signaling, and type I and type II interferon signaling. GSEA identified genes regulated by the presence of IL-10 with similar gene sets in both the model system and the patient plasma system. In the model system, GSEA and IPA in sum identified 170 genes associated with oxidative phosphorylation/mitochondrial function to be down-regulated in monocytes stimulated with meningococci. In the patient plasma system, GSEA and IPA in sum identified 122 genes associated with oxidative phosphorylation/mitochondrial dysfunction to be down-regulated by meningococcal sepsis plasma depleted for IL-10. Using IPA, we identified IL-10 to up-regulate 18 genes associated with oxidative phosphorylation/mitochondrial function that were down-regulated by N. meningitidis. Conclusions Biological processes associated with the gene expression changes in the model system of meningococcal sepsis were comparable with the results found in the patient plasma system. By combining GSEA with IPA, we discovered an inhibitory effect of N. meningitidis on genes associated with mitochondrial function and oxidative phosphorylation, and that IL-10 partially reverses this strong inhibitory effect, thereby identifying, to our knowledge, yet another group of genes where IL-10 regulates the effect of LPS. We suggest that relying on a single bioinformatics tool together with an arbitrarily chosen filtering criteria for data analysis may result in overlooking relevant biological processes and signaling pathways associated with genes differentially expressed between compared experimental conditions.

• Brusletto, Berit Sletbakk; Hellerud, Bernt C; Løberg, Else Marit; Goverud, Ingeborg Løstegaard; Vege, Åshild & Berg, Jens Petter [Vis alle 8 forfattere av denne artikkelen] (2017). Traceability and distribution of Neisseria meningitidis DNA in archived post mortem tissue samples from patients with systemic meningococcal disease. BMC Clinical Pathology. 17(1). doi: 10.1186/s12907-017-0049-9. Fulltekst i vitenarkiv Vis sammendrag

  Background The pathophysiology and outcome of meningococcal septic shock is closely associated with the plasma level of N. meningitidis lipopolysaccharides (LPS, endotoxin) and the circulating level of meningococcal DNA. The aim of the present study was to quantify the number of N. meningitidis in different formalin-fixed, paraffin-embedded (FFPE) tissue samples and fresh frozen (FF) tissue samples from patients with systemic meningococcal disease (SMD), to explore the distribution of N. meningitidis in the body. Methods DNA in FFPE and FF tissue samples from heart, lungs, liver, kidneys, spleen and brain from patients with meningococcal shock and controls (lethal pneumococcal infection) stored at variable times, were isolated. The bacterial load of N. meningitidis DNA was analyzed using quantitative real-time PCR (qPCR) and primers for the capsule transport A (ctrA) gene (1 copy per N. meningitidis DNA). The human beta-hemoglobin (HBB) gene was quantified to evaluate effect of the storage times (2-28 years) and storage method in archived tissue. Results N. meningitidis DNA was detected in FFPE and FF tissue samples from heart, lung, liver, kidney, and spleen in all patients with severe shock. In FFPE brain, N. meningitidis DNA was only detected in the patient with the highest concentration of LPS in the blood at admission to hospital. The highest levels of N. meningitidis DNA were found in heart tissue (median value 3.6 × 107 copies N. meningitidis DNA/μg human DNA) and lung tissue (median value 3.1 × 107 copies N. meningitidis DNA/μg human DNA) in all five patients. N. meningitidis DNA was not detectable in any of the tissue samples from two patients with clinical meningitis and the controls (pneumococcal infection). The quantity of HBB declined over time in FFPE tissue stored at room temperature, suggesting degradation of DNA. Conclusions High levels of N. meningitidis DNA were detected in the different tissue samples from meningococcal shock patients, particularly in the heart and lungs suggesting seeding and major proliferation of meningococci in these organs during the development of shock, probably contributing to the multiple organ failure. The age of archived tissue samples appear to have an impact on the amount of quantifiable N. meningitidis DNA.

• Hellerud, Bernt C; Olstad, Ole Kristoffer; Nielsen, Erik W.; Siebke, Anne-Marie; Skadberg, Øyvind & Thorgersen, Ebbe Billmann [Vis alle 9 forfattere av denne artikkelen] (2015). Massive organ inflammation in experimental and in clinical meningococcal septic shock. Shock. ISSN 1073-2322. 44(5), s. 458–469. doi: 10.1097/SHK.0000000000000441. Fulltekst i vitenarkiv Vis sammendrag

  Fulminant meningococcal sepsis is characterized by a massive growth of bacteria in the circulation, regarded as the primary inflammatory site, with no specific solid organ focus. Here we aimed to study the local inflammatory response in organs using a porcine model of fulminant meningococcal septic shock challenged with exponentially increasing doses of heat inactivated Neisseria meningitidis. The results were compared with those obtained in organs post mortem from three patients with lethal meningococcal septic shock. Nine patients with lethal pneumococcal disease and 14 patients with sudden infant death syndrome served as controls. Frozen tissue were thawed, homogenized and prepared for quantification of bacterial DNA by real-time polymerase chain reaction, and key inflammatory mediators were measured by ELISA in the pig material and by multiplex in the human material. In addition, gene expression assayed by Affymetrix gene expression profiling was performed in the pig study. The porcine model revealed a major influx of N. meningitidis in lungs, liver, spleen, and kidneys accompanied with major production of cardinal inflammatory mediators including tumor necrosis factor, interleukin (IL)-1[beta], IL-6, and IL-8, far exceeding the amount detected in blood. Genes encoding for these mediators revealed a similar profile. By comparing the wild-type with a lipopolysaccharide (LPS) deficient meningococcal strain, we documented that LPS was the dominant group of molecules inducing organ inflammation and was required for IL-8 production. IL-10 production was predominantly stimulated by non-LPS molecules. The massive organ inflammation in the porcine model was present in the three patients dying of meningococcal shock and differed markedly from the patients with lethal pneumococcal infections and sudden infant death syndrome. In conclusion, in meningococcal sepsis, a massive local inflammatory response occurs in specific organs.

• Gopinathan, Unni; Brusletto, Berit Sletbakk; Olstad, Ole Kristoffer; Kierulf, Peter; Berg, Jens Petter & Brandtzæg, Petter [Vis alle 7 forfattere av denne artikkelen] (2015). IL-10 immunodepletion from meningococcal sepsis plasma induces extensive changes in gene expression and cytokine release in stimulated human monocytes. Innate Immunity. ISSN 1753-4259. 21(4), s. 429–449. doi: 10.1177/1753425914547743. Fulltekst i vitenarkiv
• Hellum, Marit Synnøve; Øvstebø, Reidun; Brusletto, Berit Sletbakk; Berg, Jens Petter; Brandtzæg, Petter & Henriksson, Carola (2014). Microparticle-associated tissue factor activity correlates with plasma levels of bacterial lipopolysaccharides in meningocoocal septic shock. Thrombosis Research. ISSN 0049-3848. 133(3), s. 507–514. doi: 10.1016/j.thromres.2013.12.031. Fulltekst i vitenarkiv
• Øvstebø, Reidun; Hellum, Marit Synnøve; Aass, Hans Christian; Siebke, Anne-Marie; Brandtzæg, Petter & Mollnes, Tom Eirik [Vis alle 7 forfattere av denne artikkelen] (2014). Microparticle-associated tissue factor activity is reduced by inhibition of the complement protein 5 in Neisseria meningitidis-exposed whole blood. Innate Immunity. ISSN 1753-4259. 20(5), s. 552–560. doi: 10.1177/1753425913502099. Fulltekst i vitenarkiv
• Tønjum, Tone; Brandtzæg, Petter & Henriques-Normark, B (2013). Meningitis. I Rosenberg, Eugene; DeLang, Edvard F.; Lory, Stephen; Stackebrandt, Erko & Thompsen, Fabiano (Red.), The prokaryotes - Human Microbiology. Springer. ISSN 9783642301452. s. 401–427. doi: 10.1007/978-3-642-30144-5_106. Fulltekst i vitenarkiv
• Gopinathan, Unni; Øvstebø, Reidun; Olstad, Ole Kristoffer; Brusletto, Berit Sletbakk; Aass, Hans Christian & Kierulf, Peter [Vis alle 8 forfattere av denne artikkelen] (2012). Global Effect of Interleukin-10 on the Transcriptional Profile Induced by Neisseria meningitidis in Human Monocytes. Infection and Immunity. ISSN 0019-9567. 80(11), s. 4046–4054. doi: 10.1128/IAI.00386-12. Fulltekst i vitenarkiv
• Kvakkestad, Kristin Marie; Gammelsrud, Karianne Wiger; Brandtzæg, Petter & Høiby, Ernst Arne (2012). Unchanged Antibiotic Susceptibility in Escherichia coli and Pseudomonas aeruginosa after Long-Term in vitro Exposure to Antineoplastic Drugs. Chemotherapy. ISSN 0009-3157. 58(2), s. 118–122. doi: 10.1159/000337058. Fulltekst i vitenarkiv
• Hellum, Marit Synnøve; Øvstebø, Reidun; Siebke, Anne-Marie; Berg, Jens Petter; Brandtzæg, Petter & Henriksson, Carola (2012). Microparticle-associated tissue factor activity measured with the Zymuphen MP-TF kit and the calibrated automated thrombogram assay. Blood Coagulation and Fibrinolysis. ISSN 0957-5235. 23(6), s. 520–526. doi: 10.1097/MBC.0b013e328354a256. Fulltekst i vitenarkiv
• Øvstebø, Reidun; Aass, Hans Christian; Foss, Kari Bente; Siebke, Anne-Marie; Gopinathan, Unni & Kierulf, Peter [Vis alle 9 forfattere av denne artikkelen] (2012). LPS from Neisseria meningitidis is crucial for inducing monocyte- and microparticle-associated tissue factor activity but not for tissue factor expression. Innate Immunity. ISSN 1753-4259. 18(4), s. 580–591. doi: 10.1177/1753425911428230. Fulltekst i vitenarkiv
• Gammelsrud, Karianne Wiger; Langnes, Belinda; Gaustad, Peter; Ingebretsen, André; Høiby, Ernst Arne & Brandtzaeg, Petter [Vis alle 7 forfattere av denne artikkelen] (2012). Multilocus sequence typing of serial Candida albicans isolates from children with cancer, children with cystic fibrosis and healthy controls. Medical Mycology. ISSN 1369-3786. 50(6), s. 619–626. doi: 10.3109/13693786.2012.675088. Fulltekst i vitenarkiv
• Gammelsrud, Karianne Wiger; Sandven, Per; Høiby, Ernst Arne; Sandvik, Leiv; Brandtzæg, Petter & Gaustad, Peter (2011). Colonization by Candida in children with cancer, children with cystic fibrosis, and healthy controls. Clinical Microbiology and Infection (CMI). ISSN 1198-743X. 17(12), s. 1875–1881. doi: 10.1111/j.1469-0691.2011.03528.x. Fulltekst i vitenarkiv
• Brekke, Ole Lars; Hellerud, Bernt C; Christiansen, Dorte; Fure, Hilde; Castellheim, Albert & Nielsen, Erik Waage [Vis alle 13 forfattere av denne artikkelen] (2011). Neisseria meningitidis and Escherichia coli are protected from leukocyte phagocytosis by binding to erythrocyte complement receptor 1 in human blood. Molecular Immunology. ISSN 0161-5890. 48(15-16), s. 2159–2169. doi: 10.1016/j.molimm.2011.07.011. Fulltekst i vitenarkiv
• Brandtzæg, Petter & Deuren, Marcel van (2011). Classification and pathogenesis of meningococcal disease. I Christodoulides, Myron (Red.), Neisseria meningitidis: Advances Methods and Protocols (Methods in Molecular Biology). Humana Press. ISSN 9781617793455. s. 21–35. doi: 10.1007/978-1-61779-346-2_2. Fulltekst i vitenarkiv
• Rasmussen, Inge; Wallace, Sean Ciaran; Mengshoel, Anne Torunn; Høiby, Ernst Arne & Brandtzæg, Petter (2011). Diphtheria outbreak in Norway: Lessons learned. Scandinavian Journal of Infectious Diseases. ISSN 0036-5548. 43(11-12), s. 986–989. doi: 10.3109/00365548.2011.600326. Fulltekst i vitenarkiv
• Hellerud, Bernt Christian; Aase, Audun; Herstad, Tove Karin; Næss, Lisbeth Meyer; Kristiansen, Lisa Høyem & Siebke, Anne-Marie [Vis alle 11 forfattere av denne artikkelen] (2010). Critical roles of complement and antibodies in host defense mechanisms against Neisseria meningitidis as revealed by human complement genetic deficiencies. Infection and Immunity. ISSN 0019-9567. 78(2), s. 802–809. doi: 10.1128/IAI.01044-09. Fulltekst i vitenarkiv
• Krogh, Kristin; Surén, Pål; Mengshoel, Anne T & Brandtzæg, Petter (2010). Tuberculosis among children in Oslo, Norway, from 1998 to 2009. Scandinavian Journal of Infectious Diseases. ISSN 0036-5548. 42(11-12), s. 866–872. doi: 10.3109/00365548.2010.508461. Fulltekst i vitenarkiv
• Hellerud, Bernt C; Nielsen, Erik Waage; Thorgersen, Ebbe Billmann; Lindstad, Julie Katrine; Pharo, Anne Margrethe & Tønnessen, Tor Inge [Vis alle 9 forfattere av denne artikkelen] (2010). Dissecting the effects of lipopolysaccharides from nonlipopolysaccharide molecules in experimental porcine meningococcal sepsis. Critical Care Medicine. ISSN 0090-3493. 38(6), s. 1467–1474. doi: 10.1097/CCM.0b013e3181de8c94. Fulltekst i vitenarkiv
• Nielsen, Erik Waage; Hellerud, BC; Thorgersen, Ebbe B; Castellheim, A; Pharo, A & Lindstad, Julie [Vis alle 10 forfattere av denne artikkelen] (2009). A NEW DYNAMIC PORCINE MODEL OF MENINGOCOCCAL SHOCK. Shock. ISSN 1073-2322. 32(3), s. 302–309. doi: 10.1097/SHK.0b013e31819c37be. Fulltekst i vitenarkiv
• Hellerud, BC; Stenvik, Jørgen; Espevik, Terje; Lambris, John D.; Mollnes, Tom Eirik & Brandtzaeg, P (2008). Stages of meningococcal sepsis stimulated in vitro, with emphasis on complement and Toll-like receptor activation. Infection and Immunity. ISSN 0019-9567. 76(9), s. 4183–4189. Fulltekst i vitenarkiv
• Øvstebø, Reidun; Olstad, Ole Kristoffer; Brusletto, Berit; Møller, Anne Sophie; Aase, Audun & Haug, Kari Bente Foss [Vis alle 8 forfattere av denne artikkelen] (2008). Identification of genes particularly sensitive to lipopolysaccharide (LPS) in human monocytes induced by wild-type versus LPS-Deficient Neisseria meningitidis strains. Infection and Immunity. ISSN 0019-9567. 76(6), s. 2685–2695. doi: 10.1128/IAI.01625-07. Fulltekst i vitenarkiv
• Hellerud, BC; Stenvik, Jørgen; Espevik, Terje; Lambris, JD; Mollnes, TE & Brandtzæg, Petter (2008). Stages of meningococcal sepsis simulated in vitro, with emphasis on complement and Toll-like receptor activation. Infection and Immunity. ISSN 0019-9567. 76(9), s. 4183–4189. doi: 10.1128/IAI.00195-08. Fulltekst i vitenarkiv
• Rojahn, Astrid; Brusletto, Berit Sletbakk; Øvstebø, Reidun; Foss, Kari Bente; Kierulf, Peter & Brandtzæg, Petter (2008). Does granulocyte colony-stimulating factor ameliorate the proinflammatory response in human meningococcal septic shock? Critical Care Medicine. ISSN 0090-3493. 36, s. 2583–2589. doi: 10.1097/CCM.0b013e3181844399. Fulltekst i vitenarkiv
• Stephens, DS; Greenwood, B & Brandtzæg, Petter (2007). Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. The Lancet. ISSN 0140-6736. 369. Fulltekst i vitenarkiv
• Møller, A; Bjerre, Anna; Brusletto, B; Joø, G. B.; Brandtzæg, Petter & Kierulf, Peter (2005). Chemokine patterns in meningococcal disease. Journal of Infectious Diseases. ISSN 0022-1899. 191, s. 768–775. Fulltekst i vitenarkiv
• Møller, Anne-Sophie Wiborg; Bjerre, Anna Kristina; Brusletto, Berit Sletbakk; Joø, Gun Brit; Brandtzæg, Petter & Kierulf, Peter (2005). Chemokine Pattern in Meningococcal Disease. Journal of Infectious Diseases. ISSN 0022-1899. 191(5), s. 768–775. Fulltekst i vitenarkiv Vis sammendrag

  Chemokines are important in regulating leukocyte traffic during infection. We analyzed plasma chemokine levels of monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1 alpha , interleukin (IL)-8, and RANTES in patients with meningococcal infection and correlated these to plasma lipopolysaccharide (LPS) levels, which are closely associated with clinical presentation. In patients with fulminant meningococcal septicemia, versus distinct meningitis or mild systemic meningococcal disease, MCP-1 (both P<.0001), MIP-1 alpha (both P<.0001), and IL-8 (P<.0001 and P=.011) were significantly higher and RANTES significantly lower (P=.007 and P=.021). MCP-1 (r=.88), MIP-1 alpha (r=.82), and IL-8 (r=.89) were positively correlated to plasma LPS levels, whereas RANTES was negatively correlated (r=-.49). In an ex vivo whole-blood model, heat-inactivated wild-type Neisseria meningitidis, purified meningococcal LPS, and (to a negligible extent) heat-inactivated LPS-deficient mutant N. meningitidis induced these chemokines. N. meningitidis LPS is the major cause of chemokine release in meningococcal disease.

• Sprong, T; Møller, AS; Bjerre, A; Wedege, Elisabeth; Kierulf, P & Meer, JW van der [Vis alle 9 forfattere av denne artikkelen] (2004). Complement activation and complement-dependent inflammation by Neisseria meningitidis are independent of lipopolysaccharide. Infection and Immunity. ISSN 0019-9567. 72, s. 3344–3349. Fulltekst i vitenarkiv
• Sprong, T.; Møller, Anne-Sophie Wiborg; Bjerre, Anna Kristina; Wedege, E.; Kierulf, Peter & Meer, J. W. M.* van der [Vis alle 9 forfattere av denne artikkelen] (2004). Complement activation and complement-dependent inflammation by Neisseria meningitidis are independent of lipopolysaccharide. Infection and Immunity. ISSN 0019-9567. 72(6), s. 3344–3349. Fulltekst i vitenarkiv Vis sammendrag

  Fulminant meningococcal sepsis has been termed the prototypical lipopolysaccharide (LPS)-mediated gram-negative septic shock. Systemic inflammation by activated complement and cytokines is important in the pathogenesis of this disease. We investigated the involvement of meningococcal LPS in complement activation, complement-dependent inflammatory effects, and cytokine or chemokine production. Whole blood anticoagulated with lepirudin was stimulated with wild-type Neisseria meningitidis H44/76 (LPS+), LPS-deficient N. meningitidis H44/76lpxA (LPS�), or purified meningococcal LPS (NmLPS) at concentrations that were relevant to meningococcal sepsis. Complement activation products, chemokines, and cytokines were measured by enzyme-linked immunosorbent assays, and granulocyte CR3 (CD11b/CD18) upregulation and oxidative burst were measured by flow cytometry. The LPS+ and LPS� N. meningitidis strains both activated complement effectively and to comparable extents. Purified NmLPS, used at a concentration matched to the amount present in whole bacteria, did not induce any complement activation. Both CR3 upregulation and oxidative burst were also induced, independent of LPS. Interleukin-1ß (IL-1ß), tumor necrosis factor alpha, and macrophage inflammatory protein 1 production was predominantly dependent on LPS, in contrast to IL-8 production, which was also markedly induced by the LPS� meningococci. In this whole blood model of meningococcal sepsis, complement activation and the immediate complement-dependent inflammatory effects of CR3 upregulation and oxidative burst occurred independent of LPS.

• Bjerre, Anna Kristina; Brusletto, Berit Sletbakk; Høiby, Ernst Arne; Kierulf, Peter & Brandtzæg, Petter (2004). Plasma interferon-gamma and interleukin-10 concentrations in systemic meningococcal disease compared with severe systemic Gram-positive septic shock. Critical Care Medicine. ISSN 0090-3493. 32, s. 433–438. Fulltekst i vitenarkiv Vis sammendrag

  OBJECTIVE: To analyze plasma interferon-gamma and interleukin-10 concentrations in patients with systemic meningococcal disease and patients with severe Gram-positive septic shock caused by Streptococcus pneumoniae or Staphylococcus aureus. To study the in vitro cytokine (interferon-gamma and interleukin-10) responses in a whole blood model boosted with heat-killed Neisseria meningitidis, S. pneumoniae, and S. aureus before and after treatment with recombinant interleukin-10 or recombinant interferon-gamma. DESIGN: Experimental study. SETTING: Laboratory. SUBJECTS: Plasma samples were collected from patients with systemic meningococcal disease (n = 66) and patients with severe Gram-positive septic shock caused by S. pneumoniae (n = 4) or S. aureus (n = 3). INTERVENTIONS: Whole blood was boosted with heat-killed N. meningitidis, S. pneumoniae, and S. aureus (1 x 106 colony forming units/mL), and plasmas were analyzed for interleukin-10 or interferon-gamma at 0, 5, 12, and 24 hrs. Furthermore, recombinant interleukin-10 or recombinant interferon-gamma was added before bacteria, and the effect on the secretion of interferon-gamma and interleukin-10, respectively, was analyzed after 24 hrs. MEASUREMENTS AND MAIN RESULTS: The median concentration of interferon-gamma was 15 pg/mL and of interleukin-10 was 10,269 pg/mL in patients with meningococcal septic shock (n = 24) compared with median interferon-gamma concentration of 3400 pg/mL and interleukin-10 concentration of 465 pg/mL in patients with severe Gram-positive shock (p =.001). Increased interferon-gamma concentrations were associated with case fatality (p =.011). In a whole blood model we demonstrated that 1 x 106 colony forming units/mL of N. meningitidis induced more interleukin-10 but less interferon-gamma than S. pneumoniae. S. aureus induced minimal secretion of both cytokines. Recombinant interleukin-10 efficiently down-regulated the secretion of interferon-gamma, and vice versa, as shown in a whole blood model. CONCLUSION: We speculate whether high concentrations of interleukin-10 contribute to the low concentrations of interferon-gamma in fulminant meningococcal septicemia. In addition, it appears as if interferon-gamma plays a minor role in the pathophysiology of meningococcal septic shock

• Brandtzæg, Petter (2004). Aktivert protein C ved sepsis (Editorial). Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 124, s. 766–766. Fulltekst i vitenarkiv
• Øvstebø, Reidun; Brandtzæg, Petter; Brusletto, Berit Sletbakk; Foss, Kari Bente; Lande, Knut & Høiby, EA [Vis alle 7 forfattere av denne artikkelen] (2004). Use of robotized DNA isolation and real-time PCR to quantify and identify close correlation between levels of Neisseria meningitidis DNA and lipopolysaccharides in plasma and cerebrospinal fluid from patients with systemic meningococcal disease. Journal of Clinical Microbiology. ISSN 0095-1137. 42, s. 2980–2987. Fulltekst i vitenarkiv
• Sprong, Tom; Brandtzaeg, Petter; Fung, Michael; Pharo, Anne; Høiby, Ernst Arne & Michaelsen, Terje Einar [Vis alle 10 forfattere av denne artikkelen] (2003). Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis. Blood. ISSN 0006-4971. 102, s. 3702–3710. Fulltekst i vitenarkiv Vis sammendrag

  The complement system plays an important role in the initial defense against Neisseria meningitidis. In contrast, uncontrolled activation in meningococcal sepsis contributes to the development of tissue damage and shock. In a novel human whole blood model of meningococcal sepsis, we studied the effect of complement inhibition on inflammation and bacterial killing. Monoclonal antibodies (mAbs) blocking lectin and alternative pathways inhibited complement activation by N meningitidis and oxidative burst induced in granulocytes and monocytes. Oxidative burst was critically dependent on CD11b/CD18 (CR3) expression but not on Fc gamma-receptors. Specific inhibition of C5a using mAb 137-26 binding the C5a moiety of C5 before cleavage prohibited CR3 up-regulation, phagocytosis, and oxidative burst but had no effect on C5b-9 (TCC) formation, lysis, and bacterial killing. An mAb-blocking cleavage of C5, preventing C5a and TCC formation, showed the same effect on CR3, phagocytosis, and oxidative burst as the anti-C5a mAb but additionally inhibited TCC formation, lysis, and bacterial killing, consistent with a C5b-9-dependent killing mechanism. In conclusion, the anti-C5a mAb 137-26 inhibits the potentially harmful effects of N meningitidis-induced C5a formation while preserving complement-mediated bacterial killing. We suggest that this may be an attractive approach for the treatment of meningococcal sepsis

• Brandtzæg, Petter (2003). The inflammatory response induced by Neisseria meningitidis completely lacking endotoxin. Expert Review of Anti-Infective Therapy. ISSN 1478-7210. 1, s. 89–96. Fulltekst i vitenarkiv
• Bjerre, Anna; Brusleto, Berit; Øvstebø, Reidun; Joø, Gun Britt; Kierulf, Peter & Brandtzæg, Petter (2003). Idenfication of meningococcal LPS as a major monocyte activator in IL-10 depleted shock plasmas and CSF by blocking the CD14-TLR4 receptor complex. Journal of Endotoxin Research. ISSN 0968-0519. 9, s. 155–163. Fulltekst i vitenarkiv
• Brandtzæg, Petter (2003). Meningococcal disease. I Warrell, David A; Cox, Timothy M; Firth, John D & Jr., Edward J Benz (Red.), Oxford Textbook of Medicine, 4th Edition. Oxford University Press. s. 478–485. Fulltekst i vitenarkiv
• Sprong, T.; Brandtzæg, Petter; Fung, M.; Pharo, Anne Margrethe; Høiby, Ernst Arne & Michaelsen, Terje Einar [Vis alle 10 forfattere av denne artikkelen] (2003). Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis. Blood. ISSN 0006-4971. 102, s. 3702–3710. Fulltekst i vitenarkiv
• Bjerre, A; Brusletto, B; Mollnes, TE; Fritzsønn, Elisabeth; Rosenqvist, Einar & Wedege, Elisabeth [Vis alle 9 forfattere av denne artikkelen] (2002). Complement activation induced by purified Neisseria meningitidis lipopolysaccharide (LPS), outer mebrane vesicles, whole bacteria, and an LPS-free mutant. Journal of Infectious Diseases. ISSN 0022-1899. 185, s. 220–228. Fulltekst i vitenarkiv
• Brandtzæg, Petter & Deuren, Marcel Van (2002). Current concepts in the role of the hostresponse in Neisseria meningitidis septic shock. Current Opinion in Infectious Diseases. ISSN 0951-7375. 15, s. 247–252. Fulltekst i vitenarkiv
• Iversen, Nina; Kierulf, Peter; Brandtzæg, Petter; Sandset, Per Morten & Abildgaard, Ulrich (2002). TFPI fractions in plasma from patients with systemic meningococcal disease. Thrombosis Research. ISSN 0049-3848. 108(5-6), s. 347–353. Fulltekst i vitenarkiv
• Namork, Ellen & Brandtzæg, Petter (2002). Fatal meningococcal septicaemia with "blebing" meningococcus. The Lancet. ISSN 0140-6736. 360, s. 1741–1741. Fulltekst i vitenarkiv
• Brandtzæg, Petter; Bjerre, Anna; Øvstebø, Reidun; Joø, Gun Britt; Brusletto, B. & Kierulf, Peter [Vis alle 7 forfattere av denne artikkelen] (2001). Neisseria meningitidis lipopolysaccahrides in human pathology. Journal of Endotoxin Research. ISSN 0968-0519. 7, s. 401–420. Fulltekst i vitenarkiv
• Brandtzæg, Petter; Bjerre, Anna; Øvstebø, Reidun; Brusleto, Berit; Joø, Gun Britt & Kierulf, Peter (2001). Neisseria meningitidis lipopolysaccharides in human pathology. Journal of Endotoxin Research. ISSN 0968-0519. 7(6), s. 401–420. Fulltekst i vitenarkiv
• Brandtzæg, Petter (2001). Infeksiøse barnesykdommer. I Vennerød, Anne Marie (Red.), Norsk legemiddelhåndbok for helsepersonell 2001. Foreningen for utgivelse av Norsk legemiddelhåndbok. s. 32–36. Fulltekst i vitenarkiv
• Deuren, Marcel van & Brandtzæg, Petter (2001). Cytokine measurement in vivo and in vitro. I Pollard, Andrew J. & Maiden, Martin CJ (Red.), Methods in Moleculare Medicine, meningococcal disease. Humana Press, Totowa, New Jersey, USA. ISSN 9780896038493. s. 459–486. Fulltekst i vitenarkiv
• Brandtzæg, Petter; Øvstebø, Reidun & Kierulf, Peter (2001). Quantitative detection of bacterial lipopolysaccharides in clinical specimens. I Pollard, Andrew J. & Maiden, Martin CJ (Red.), Methods in Moleculare Medicine, meningococcal disease. Humana Press, Totowa, New Jersey, USA. ISSN 9780896038493. s. 427–439. Fulltekst i vitenarkiv
• Deuren, Marcel van; Brandtzæg, Petter & Meer, Jos W. M. van der (2000). Update on meningococcal disease with emphasis on pathogenesis and clinical management. Clinical Microbiology Reviews. ISSN 0893-8512. 13(1), s. 144–166. Fulltekst i vitenarkiv
• Bjerre, Anna; Øvstebø, Reidun; Kierulf, Peter; Halvorsen, Sverre & Brandtzæg, Petter (2000). Fulminant Meningococcal Septicemia:Dissociation between Plasma Thrombopoietin Levels and Platelet Counts. Clinical Infectious Diseases. ISSN 1058-4838. 30, s. 643–647. Fulltekst i vitenarkiv
• Brandtzæg, Petter; Øvstebø, Reidun & Kierulf, Peter (2000). Quantitative detection of bacterial lipopolysaccharides in clinical specimens, Methods in Molecular Medicine Meningococcal Disease. Humana Press, USA. Fulltekst i vitenarkiv

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• Hellerud, Bernt C; Aase, Audun; Næss, Lisbeth Meyer; Nome, Lisa; Herstad, Tove Karin & Lappegaard, Knut Tore [Vis alle 10 forfattere av denne artikkelen] (2011). Vaccination of a C5-deficient man against Neisseria meningitidis: Effect on opsonophagocytosis and bacterial growth. Molecular Immunology. ISSN 0161-5890. 48(14), s. 1711–1711. doi: 10.1016/j.molimm.2011.06.365. Fulltekst i vitenarkiv
• Hellerud, Bernt C; Olstad, Ole Kristoffer; Brandtzæg, Petter & Mollnes, Tom Eirik (2009). Transcription of key components of complement and the TLR-signaling system is down-regulated by LPS in a porcine model of meningococcal sepsis. Molecular Immunology. ISSN 0161-5890. 46(14), s. 2853–2854. doi: 10.1016/j.molimm.2009.05.283. Fulltekst i vitenarkiv
• Kristiansen, bjØrn-erik; Brandtzæg, Petter; Bjorvatn, Bjarne; Bjorvatn, Bjarne & Solberg, Claus Ola (2009). Meningokokkvaksineforsøket 1988-91. 129(3), s. 192–194. Fulltekst i vitenarkiv
• Ovstebo, R; Haug, KBF; Henriksson, C; Aass, HCD; Troseid, AMS & Olstad, OK [Vis alle 9 forfattere av denne artikkelen] (2009). MicroRNA patterns in human monocytes induced by wildtype versus LPS deficient neisseria meningitides-Relationship between microRNA and LPS sensitive genes. Cytokine. ISSN 1043-4666. 48(1-2), s. 114–114. doi: 10.1016/j.cyto.2009.07.483. Fulltekst i vitenarkiv
• Gopinathan, U; Ovstebo, R; Olstad, OK; Kierulf, Peter; Brandtzæg, Petter & Berg, Jens Petter (2009). Interleukin-10 inhibits expression of genes induced by wild-type Neisseria meningitidis in human monocytes. Cytokine. ISSN 1043-4666. 48(1-2), s. 114–114. doi: 10.1016/j.cyto.2009.07.482. Fulltekst i vitenarkiv
• Hellerud, Bernt Christian; Høiby, Ernst Arne; Lappegård, Knut Tore; Fure, Hilde; Brandtzæg, Petter & Harboe, Morten [Vis alle 7 forfattere av denne artikkelen] (2007). Human genetic complement deficiencies reveal a critical role for C5/C5a in the phagocytosis and killing of Neisseria meningitidis and Escherichia coli in whole blood. Molecular Immunology. ISSN 0161-5890. 44(16), s. 3978–3978. doi: 10.1016/j.molimm.2007.06.180. Fulltekst i vitenarkiv
• Hellerud, Bernt C; Thorgersen, Ebbe Billmann; Castellheim, Albert; Nielsen, EW; Pharo, Anne Margrethe & Lindstad, Julie Katrine [Vis alle 10 forfattere av denne artikkelen] (2007). The role of complement and CD14 in the Gram-negative bacteria induced inflammatory reaction: In vitro evidence and design of an in vivo porcine model. Molecular Immunology. ISSN 0161-5890. 44, s. 182–182. doi: 10.1016/j.molimm.2006.07.085. Fulltekst i vitenarkiv
• Deuren, M van & Brandtzæg, Petter (2005). Myocardial dysfunction in meningococcal septic shock: No clear answer yet. Critical Care Medicine. ISSN 0090-3493. 33. Fulltekst i vitenarkiv
• Brandtzæg, Petter (2005). Recently discovered virus--known symptoms. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 125(20). Fulltekst i vitenarkiv
• Brandtzæg, Petter (2002). Bedre helse uten eliteforskning? Aftenposten (morgenutg. : trykt utg.). ISSN 0804-3116. s. 14–14. Fulltekst i vitenarkiv
• Brandtzæg, Petter (2002). Forskningsråd mot storting: helse nedprioriteres. Aftenposten (morgenutg. : trykt utg.). ISSN 0804-3116. s. 8–8. Fulltekst i vitenarkiv
• Brandtzæg, Petter (2002). Patofysiologi ved bakteriell meningitt. Fulltekst i vitenarkiv
• Brandtzæg, Petter (2002). Overwhelming meningococcal septic shock - what is new? Fulltekst i vitenarkiv
• Brandtzæg, Petter; Bjerre, Anna; Øvstebø, Reidun; Joø, Gun Britt; Møller, A. S. & Kierulf, Peter (2002). Meningococcal infections - from clinical observation to molecular dissection. Fulltekst i vitenarkiv
• Bergsaker, Marianne; Brandtzæg, Petter & Caugant, Dominique A (2002). Prevalence of bacterial meningitis in Nepal. Fulltekst i vitenarkiv
• Øvstebø, Reidun; Brusleto, Berit; Haug, Kari Bente Foss; Kierulf, Peter; Bjerre, Anna & Brandtzæg, Petter (2002). Quantitative estimates of Neisseria meningitidis DNA (Nm-DNA) in plasma and CSF from patients with systemic meningococcal disease (SMD)correlate with LAL quantified LPS. Fulltekst i vitenarkiv
• Bjerre, Anna; Brusleto, Berit; Øvstebø, Reidun; Joø, Gun Britt; Kierulf, Peter & Brandtzæg, Petter (2002). Identification of meningococcal LPS as a major monocyte activator in IL-10 depleted shock plasma and CSF by blocking the CD14-TLR4 receptor complex. Fulltekst i vitenarkiv
• Øvstebø, Reidun; Brusleto, Berit; Haug, Kari Bente Foss; Kierulf, Peter; Bjerre, Anna & Brandtzæg, Petter (2002). Quantitative association between plasma LPS and load of bacterial DNA in systemic meningococcal disease as evaluated by robotisized quantitative PCR. Fulltekst i vitenarkiv
• Møller, A. S.; Bjerre, Anna; Brusleto, Berit; Brandtzæg, Petter & Kierulf, Peter (2002). MCP-1 and MIP-1a in patients with systemic meningococcal disease. Fulltekst i vitenarkiv
• Sprong, T.; Møller, A. S.; Kierulf, Peter; Wedege, Elisabeth; Deuren, Marcel van & Meer, J. van der [Vis alle 8 forfattere av denne artikkelen] (2001). Complement activation and complement-dependent inflammatory effects induced by Neisseria meningitidis occur independently of lipopolysaccharide (LPS). Fulltekst i vitenarkiv Vis sammendrag

  Abstract not available.

• Brandtzæg, Petter; Bjerre, Anna; Øvstebø, Reidun; Brusleto, Berit & Kierulf, Peter (2001). Er septisk sjokk plasma antiinflammatorisk? Fulltekst i vitenarkiv
• Brandtzæg, Petter (2001). Patofysiologi ved sepsis. Fulltekst i vitenarkiv
• Brandtzæg, Petter (2001). The pathophysiology of meningococcal infections. Fulltekst i vitenarkiv
• Brandtzæg, Petter; Bjerre, Anna; Øvstebø, Reidun; Brusleto, Berit & Kierulf, Peter (2001). Meningococcal disease: from benign meningococcemia to fatal sepsis. Fulltekst i vitenarkiv
• Brandtzæg, Petter (2001). The role of endotoxin in meningococcal infections. Fulltekst i vitenarkiv
• Brandtzæg, Petter (2001). Meningococcal infections. Clinical manifestations and pathophysiological background. Fulltekst i vitenarkiv
• Brandtzæg, Petter; Bjerre, Anna; Øvstebø, Reidun; Brusleto, Berit & Kierulf, Peter (2001). What initiates the transition from sepsis to hyper- and hypodynamic septic shock. Fulltekst i vitenarkiv
• Brandtzæg, Petter; Bjerre, Anna; Øvstebø, Reidun; Brusleto, Berit & Kierulf, Peter (2001). What initiates the transition from sepsis to hyper- og hypodynamic septic shock ? Fulltekst i vitenarkiv
• Brandtzæg, Petter; Bjerre, Anna; Øvstebø, Reidun; Brusleto, Berit & Kierulf, Peter (2001). Meningococcal disease: From benign meningo-coccemia to fatal sepsis. Fulltekst i vitenarkiv
• Kierulf, Peter; Bjerre, Anna; Øvstebø, Reidun; Joø, Gun Britt; Rosenqvist, Einar & Namork, Ellen [Vis alle 8 forfattere av denne artikkelen] (2001). Cellular and humoral responses of membrane-bound meningococcal LPS. Fulltekst i vitenarkiv
• Iversen, Nina; Brandtzæg, Petter & Abildgaard, Ulrich (2001). Consumption of the factor Xa-TFPI complex in meningococcal septicemia. Fulltekst i vitenarkiv
• Kierulf, Peter; Bjerre, Anna; Brusleto, Berit; Øvstebø, Reidun; Joø, Gun Britt & Rosenqvist, Einar [Vis alle 9 forfattere av denne artikkelen] (2001). Cellular and humoral responses of membrane-bound meningococcal LPS. Fulltekst i vitenarkiv
• Bjerre, Anna; Brusleto, Berit; Øvstebø, Reidun; Rosenqvist, Einar; Namork, Ellen & Mollnes, Tom Eirik [Vis alle 8 forfattere av denne artikkelen] (2000). Cellulære og humorale reaksjoner på membranbundet meningokokk LPS. Fulltekst i vitenarkiv
• Deuren, Marcel van & Brandtzæg, Petter (2000). Parents' and GPs' key role in diagnosis of meningococcal septicaemia. The Lancet. ISSN 0140-6736. 356, s. 954–955. Fulltekst i vitenarkiv
• Bjerre, Anna; Brusleto, Berit; Øvstebø, Reidun; Rosenqvist, Einar; Namork, Ellen & Kierulf, Peter [Vis alle 7 forfattere av denne artikkelen] (2000). Cellebundet endotoxin: er det av betydning? Fulltekst i vitenarkiv
• Bjerre, Anna; Brusleto, Berit; Øvstebø, Reidun; Rosenqvist, Einar; Namork, Ellen & Kierulf, Peter [Vis alle 7 forfattere av denne artikkelen] (2000). Cellular responses of membrane-bound meningocccal LPS. Fulltekst i vitenarkiv
• Bjerre, Anna; Brusleto, Berit; Øvstebø, Reidun; Rosenqvist, Einar; Namork, Ellen & Kierulf, Peter [Vis alle 7 forfattere av denne artikkelen] (2000). Cellular responses of membrane-bound meningococcal lipopolysaccharides. Fulltekst i vitenarkiv
• Bjerre, Anna; Brusleto, Berit; Rosenqvist, Einar; Namork, Ellen; Mollnes, Tom Eirik & Kierulf, Peter [Vis alle 7 forfattere av denne artikkelen] (2000). Complement activation of membrane-bound meningococcal LPS. Fulltekst i vitenarkiv
• Bjerre, Anna; Brusleto, Berit; Øvstebø, Reidun; Kierulf, Peter & Brandtzæg, Petter (2000). Is lipid A the principal monocyte activating factor in meningococcal septic shock plasma? Fulltekst i vitenarkiv
• Bjerre, Anna; Brandtzæg, Petter & Halvorsen, Sverre (1999). Thrombopoietin (TPO) hos barn og ungdommer. Fulltekst i vitenarkiv
• Hellerud, Bernt C & Brandtzæg, Petter (2011). Meningococcal sepsis: : Beneficial and harmful inflammatory mechanisms. Universitetet i Oslo. Fulltekst i vitenarkiv

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