Petter Brandtzæg

• 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. ISSN 2235-2988. 13, p. 1–10. doi: 10.3389/fcimb.2023.1298360. Full text in Research Archive
• 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. ISSN 2235-2988. 12, p. 1–19. doi: 10.3389/fcimb.2022.908204. Full text in Research Archive Show summary

  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 [Show all 9 contributors for this article] (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. ISSN 2235-2988. 10:42, p. 1–30. doi: 10.3389/fcimb.2020.00042. Full text in Research Archive
• Mihret, Wude; Brusletto, Berit Sletbakk; Øvstebø, Reidun; Siebke, Anne-Marie; Norheim, Gunnstein & Merid, Yared [Show all 15 contributors for this article] (2019). Molecular studies of meningococcal and pneumococcal meningitis patients in Ethiopia. Innate Immunity. ISSN 1753-4259. 25(3), p. 158–167. doi: 10.1177/1753425918806363. Full text in Research Archive
• Aass, Hans Christian Dalsbotten; Hellum, Marit Synnøve; Siebke, Anne-Marie; Brandtzæg, Petter; Berg, Jens Petter & Øvstebø, Reidun [Show all 7 contributors for this article] (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), p. 101–111. doi: 10.1177/1753425917749299. Full text in Research Archive
• Gopinathan, Unni; Redalen, Kathrine; Siebke, Anne-Marie; Kierulf, Peter; Brandtzæg, Petter & Ree, Anne Hansen [Show all 8 contributors for this article] (2018). Large-scale reduction of tyrosine kinase activities in human monocytes stimulated in vitro with N. meningitidis. PLOS ONE. ISSN 1932-6203. 13(1). doi: 10.1371/journal.pone.0181912. Full text in Research Archive
• Knudsen, Per Kristian; Brandtzæg, Petter; Høiby, Ernst Arne; Bohlin, Jon; Samuelsen, Ørjan & Steinbakk, Martin [Show all 9 contributors for this article] (2017). Impact of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in children in a low resistance prevalence setting. PLOS ONE. ISSN 1932-6203. 12(11). doi: 10.1371/journal.pone.0187618. Full text in Research Archive
• Gopinathan, Unni; Øvstebø, Reidun; Brusletto, Berit Sletbakk; Olstad, Ole Kristoffer; Kierulf, Peter & Brandtzæg, Petter [Show all 7 contributors for this article] (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. ISSN 1471-2172. 18:46, p. 1–17. doi: 10.1186/s12865-017-0229-5.
• Brusletto, Berit Sletbakk; Hellerud, Bernt C; Løberg, Else Marit; Goverud, Ingeborg Løstegaard; Vege, Åshild & Berg, Jens Petter [Show all 8 contributors for this article] (2017). Traceability and distribution of Neisseria meningitidis DNA in archived post mortem tissue samples from patients with systemic meningococcal disease. BMC Clinical Pathology. ISSN 1472-6890. 17(1). doi: 10.1186/s12907-017-0049-9.
• Hellerud, Bernt C; Orrem, Hilde Lang; Dybwik, Knut Gustav; Pischke, Søren Erik; Barratt-Due, Andreas & Castellheim, Albert [Show all 15 contributors for this article] (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, p. 1–9. doi: 10.1186/s40560-017-0217-0. Full text in Research Archive
• 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), p. 196–205. doi: 10.1177/1753425916684201.
• Hellerud, Bernt C; Olstad, Ole Kristoffer; Nielsen, Erik W.; Siebke, Anne-Marie; Skadberg, Øyvind & Thorgersen, Ebbe Billmann [Show all 9 contributors for this article] (2015). Massive organ inflammation in experimental and in clinical meningococcal septic shock. Shock. ISSN 1073-2322. 44(5), p. 458–469. doi: 10.1097/SHK.0000000000000441. Show summary

  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 [Show all 7 contributors for this article] (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), p. 429–449. doi: 10.1177/1753425914547743.
• Øvstebø, Reidun; Hellum, Marit Synnøve; Aass, Hans Christian; Siebke, Anne-Marie; Brandtzæg, Petter & Mollnes, Tom Eirik [Show all 7 contributors for this article] (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), p. 552–560. doi: 10.1177/1753425913502099.
• 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), p. 507–514. doi: 10.1016/j.thromres.2013.12.031.
• Tønjum, Tone; Brandtzæg, Petter & Henriques-Normark, B (2013). Meningitis. In Rosenberg, Eugene; DeLang, Edvard F.; Lory, Stephen; Stackebrandt, Erko & Thompsen, Fabiano (Ed.), The prokaryotes - Human Microbiology. Springer. ISSN 978-3642301452. p. 401–427. doi: 10.1007/978-3-642-30144-5_106.
• Gopinathan, Unni; Øvstebø, Reidun; Olstad, Ole Kristoffer; Brusletto, Berit Sletbakk; Aass, Hans Christian & Kierulf, Peter [Show all 8 contributors for this article] (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), p. 4046–4054. doi: 10.1128/IAI.00386-12.
• 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), p. 520–526. doi: 10.1097/MBC.0b013e328354a256.
• Øvstebø, Reidun; Aass, Hans Christian; Foss, Kari Bente; Siebke, Anne-Marie; Gopinathan, Unni & Kierulf, Peter [Show all 9 contributors for this article] (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), p. 580–591. doi: 10.1177/1753425911428230.
• Gammelsrud, Karianne Wiger; Langnes, Belinda; Gaustad, Peter; Ingebretsen, André; Høiby, Ernst Arne & Brandtzaeg, Petter [Show all 7 contributors for this article] (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), p. 619–626. doi: 10.3109/13693786.2012.675088.
• 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), p. 118–122. doi: 10.1159/000337058.
• 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), p. 986–989. doi: 10.3109/00365548.2011.600326.
• 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), p. 1875–1881. doi: 10.1111/j.1469-0691.2011.03528.x.
• Brekke, Ole Lars; Hellerud, Bernt C; Christiansen, Dorte; Fure, Hilde; Castellheim, Albert & Nielsen, Erik Waage [Show all 13 contributors for this article] (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), p. 2159–2169. doi: 10.1016/j.molimm.2011.07.011.
• Brandtzæg, Petter & van Deuren, Marcel (2011). Classification and pathogenesis of meningococcal disease. In Christodoulides, Myron (Eds.), Neisseria meningitidis: Advances Methods and Protocols (Methods in Molecular Biology). Humana Press. ISSN 1617793450. p. 21–35. doi: 10.1007/978-1-61779-346-2_2.
• 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), p. 866–872. doi: 10.3109/00365548.2010.508461.
• Hellerud, Bernt C; Nielsen, Erik Waage; Thorgersen, Ebbe Billmann; Lindstad, Julie Katrine; Pharo, Anne Margrethe & Tønnessen, Tor Inge [Show all 9 contributors for this article] (2010). Dissecting the effects of lipopolysaccharides from nonlipopolysaccharide molecules in experimental porcine meningococcal sepsis. Critical Care Medicine. ISSN 0090-3493. 38(6), p. 1467–1474. doi: 10.1097/CCM.0b013e3181de8c94.
• Hellerud, Bernt Christian; Aase, Audun; Herstad, Tove Karin; Næss, Lisbeth Meyer; Kristiansen, Lisa Høyem & Siebke, Anne-Marie [Show all 11 contributors for this article] (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), p. 802–809. doi: 10.1128/IAI.01044-09.
• Nielsen, Erik Waage; Hellerud, BC; Thorgersen, Ebbe B; Castellheim, A; Pharo, A & Lindstad, Julie [Show all 10 contributors for this article] (2009). A NEW DYNAMIC PORCINE MODEL OF MENINGOCOCCAL SHOCK. Shock. ISSN 1073-2322. 32(3), p. 302–309. doi: 10.1097/SHK.0b013e31819c37be.
• 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), p. 4183–4189. doi: 10.1128/IAI.00195-08.
• 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, p. 2583–2589. doi: 10.1097/CCM.0b013e3181844399.
• 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), p. 4183–4189.
• Øvstebø, Reidun; Olstad, Ole Kristoffer; Brusletto, Berit; Møller, Anne Sophie; Aase, Audun & Haug, Kari Bente Foss [Show all 8 contributors for this article] (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), p. 2685–2695. doi: 10.1128/IAI.01625-07.
• Stephens, DS; Greenwood, B & Brandtzæg, Petter (2007). Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. The Lancet. ISSN 0140-6736. 369.
• 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), p. 768–775. Show summary

  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.

• 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, p. 768–775.
• 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, p. 433–438. Show summary

  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. ISSN 0029-2001. 124.
• Øvstebø, Reidun; Brandtzæg, Petter; Brusletto, Berit Sletbakk; Foss, Kari Bente; Lande, Knut & Høiby, EA [Show all 7 contributors for this article] (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, p. 2980–2987.
• Sprong, T.; Møller, Anne-Sophie Wiborg; Bjerre, Anna Kristina; Wedege, E.; Kierulf, Peter & van der Meer, J. W. M.* [Show all 9 contributors for this article] (2004). Complement activation and complement-dependent inflammation by Neisseria meningitidis are independent of lipopolysaccharide. Infection and Immunity. ISSN 0019-9567. 72(6), p. 3344–3349. Show summary

  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.

• Sprong, T; Møller, AS; Bjerre, A; Wedege, Elisabeth; Kierulf, P & van der Meer, JW [Show all 9 contributors for this article] (2004). Complement activation and complement-dependent inflammation by Neisseria meningitidis are independent of lipopolysaccharide. Infection and Immunity. ISSN 0019-9567. 72, p. 3344–3349.
• Brandtzæg, Petter (2003). Meningococcal disease. In Warrell, David A; Cox, Timothy M; Firth, John D & Benz Jr., Edward J (Ed.), Oxford Textbook of Medicine, 4th Edition. Oxford University Press. p. 478–485.
• Sprong, T.; Brandtzæg, Petter; Fung, M.; Pharo, Anne Margrethe; Høiby, Ernst Arne & Michaelsen, Terje Einar [Show all 10 contributors for this article] (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, p. 3702–3710.
• 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, p. 155–163.
• Brandtzæg, Petter (2003). The inflammatory response induced by Neisseria meningitidis completely lacking endotoxin. Expert Review of Anti-Infective Therapy. ISSN 1478-7210. 1, p. 89–96.
• Sprong, Tom; Brandtzaeg, Petter; Fung, Michael; Pharo, Anne; Høiby, Ernst Arne & Michaelsen, Terje Einar [Show all 10 contributors for this article] (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, p. 3702–3710. Show summary

  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

• Namork, Ellen & Brandtzæg, Petter (2002). Fatal meningococcal septicaemia with "blebing" meningococcus. The Lancet. ISSN 0140-6736. 360, p. 1741–1741.
• 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), p. 347–353.
• Brandtzæg, Petter & Van Deuren, Marcel (2002). Current concepts in the role of the hostresponse in Neisseria meningitidis septic shock. Current Opinion in Infectious Diseases. ISSN 0951-7375. 15, p. 247–252.
• Bjerre, A; Brusletto, B; Mollnes, TE; Fritzsønn, Elisabeth; Rosenqvist, Einar & Wedege, Elisabeth [Show all 9 contributors for this article] (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, p. 220–228.
• Brandtzæg, Petter; Øvstebø, Reidun & Kierulf, Peter (2001). Quantitative detection of bacterial lipopolysaccharides in clinical specimens. In Pollard, Andrew J. & Maiden, Martin CJ (Ed.), Methods in Moleculare Medicine, meningococcal disease. Humana Press, Totowa, New Jersey, USA. ISSN 0-89603-849-1. p. 427–439.
• Deuren, Marcel van & Brandtzæg, Petter (2001). Cytokine measurement in vivo and in vitro. In Pollard, Andrew J. & Maiden, Martin CJ (Ed.), Methods in Moleculare Medicine, meningococcal disease. Humana Press, Totowa, New Jersey, USA. ISSN 0-89603-849-1. p. 459–486.
• Brandtzæg, Petter (2001). Infeksiøse barnesykdommer. In Vennerød, Anne Marie (Eds.), Norsk legemiddelhåndbok for helsepersonell 2001. Foreningen for utgivelse av Norsk legemiddelhåndbok. p. 32–36.
• 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), p. 401–420.
• Brandtzæg, Petter; Bjerre, Anna; Øvstebø, Reidun; Joø, Gun Britt; Brusletto, B. & Kierulf, Peter [Show all 7 contributors for this article] (2001). Neisseria meningitidis lipopolysaccahrides in human pathology. Journal of Endotoxin Research. ISSN 0968-0519. 7, p. 401–420.
• Brandtzæg, Petter; Øvstebø, Reidun & Kierulf, Peter (2000). Quantitative detection of bacterial lipopolysaccharides in clinical specimens, Methods in Molecular Medicine Meningococcal Disease. Humana Press, USA.
• 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), p. 144–166.
• 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, p. 643–647.
• Bjerre, Anna; Øvstebø, Reidun; Kierulf, Peter; Halvorsen, Sverre & Brandtzæg, Petter (1999). Transient increase of plasma thrombopoientin(TPO)in fulminant meningococcal septicaemia with consumption coagulopathy. European Paediatric Research.

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• Hellerud, Bernt C; Aase, Audun; Næss, Lisbeth Meyer; Nome, Lisa; Herstad, Tove Karin & Lappegaard, Knut Tore [Show all 10 contributors for this article] (2011). Vaccination of a C5-deficient man against Neisseria meningitidis: Effect on opsonophagocytosis and bacterial growth. Molecular Immunology. ISSN 0161-5890. 48(14), p. 1711–1711. doi: 10.1016/j.molimm.2011.06.365.
• 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), p. 2853–2854. doi: 10.1016/j.molimm.2009.05.283.
• 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), p. 114–114. doi: 10.1016/j.cyto.2009.07.482.
• Ovstebo, R; Haug, KBF; Henriksson, C; Aass, HCD; Troseid, AMS & Olstad, OK [Show all 9 contributors for this article] (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), p. 114–114. doi: 10.1016/j.cyto.2009.07.483.
• Kristiansen, bjØrn-erik; Brandtzæg, Petter; Bjorvatn, Bjarne; Bjorvatn, Bjarne & Solberg, Claus Ola (2009). Meningokokkvaksineforsøket 1988-91. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 129(3), p. 192–194.
• Hellerud, Bernt C; Thorgersen, Ebbe Billmann; Castellheim, Albert; Nielsen, EW; Pharo, Anne Margrethe & Lindstad, Julie Katrine [Show all 10 contributors for this article] (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, p. 182–182. doi: 10.1016/j.molimm.2006.07.085.
• Hellerud, Bernt Christian; Høiby, Ernst Arne; Lappegård, Knut Tore; Fure, Hilde; Brandtzæg, Petter & Harboe, Morten [Show all 7 contributors for this article] (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). doi: 10.1016/j.molimm.2007.06.180.
• Brandtzæg, Petter (2005). Recently discovered virus--known symptoms. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 125(20).
• van Deuren, M & Brandtzæg, Petter (2005). Myocardial dysfunction in meningococcal septic shock: No clear answer yet. Critical Care Medicine. ISSN 0090-3493. 33.
• Brandtzæg, Petter (2002). Bedre helse uten eliteforskning? Aftenposten (morgenutg. : trykt utg.). ISSN 0804-3116.
• Brandtzæg, Petter (2002). Forskningsråd mot storting: helse nedprioriteres. Aftenposten (morgenutg. : trykt utg.). ISSN 0804-3116.
• Brandtzæg, Petter (2002). Overwhelming meningococcal septic shock - what is new?
• Brandtzæg, Petter (2002). Patofysiologi ved bakteriell meningitt.
• Møller, A. S.; Bjerre, Anna; Brusleto, Berit; Brandtzæg, Petter & Kierulf, Peter (2002). MCP-1 and MIP-1a in patients with systemic meningococcal disease.
• Brandtzæg, Petter; Bjerre, Anna; Øvstebø, Reidun; Joø, Gun Britt; Møller, A. S. & Kierulf, Peter (2002). Meningococcal infections - from clinical observation to molecular dissection.
• Bergsaker, Marianne; Brandtzæg, Petter & Caugant, Dominique A (2002). Prevalence of bacterial meningitis in Nepal.
• 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.
• 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.
• 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.
• Sprong, T.; Møller, A. S.; Kierulf, Peter; Wedege, Elisabeth; Deuren, Marcel van & Meer, J. van der [Show all 8 contributors for this article] (2001). Complement activation and complement-dependent inflammatory effects induced by Neisseria meningitidis occur independently of lipopolysaccharide (LPS). Show summary

  Abstract not available.

• Brandtzæg, Petter (2001). The pathophysiology of meningococcal infections.
• Brandtzæg, Petter (2001). The role of endotoxin in meningococcal infections.
• Brandtzæg, Petter (2001). Meningococcal infections. Clinical manifestations and pathophysiological background.
• Brandtzæg, Petter; Bjerre, Anna; Øvstebø, Reidun; Brusleto, Berit & Kierulf, Peter (2001). Er septisk sjokk plasma antiinflammatorisk?
• Brandtzæg, Petter (2001). Patofysiologi ved sepsis.
• Brandtzæg, Petter; Bjerre, Anna; Øvstebø, Reidun; Brusleto, Berit & Kierulf, Peter (2001). What initiates the transition from sepsis to hyper- and hypodynamic septic shock.
• Brandtzæg, Petter; Bjerre, Anna; Øvstebø, Reidun; Brusleto, Berit & Kierulf, Peter (2001). Meningococcal disease: from benign meningococcemia to fatal sepsis.
• Brandtzæg, Petter; Bjerre, Anna; Øvstebø, Reidun; Brusleto, Berit & Kierulf, Peter (2001). What initiates the transition from sepsis to hyper- og hypodynamic septic shock ?
• Brandtzæg, Petter; Bjerre, Anna; Øvstebø, Reidun; Brusleto, Berit & Kierulf, Peter (2001). Meningococcal disease: From benign meningo-coccemia to fatal sepsis.
• Kierulf, Peter; Bjerre, Anna; Øvstebø, Reidun; Joø, Gun Britt; Rosenqvist, Einar & Namork, Ellen [Show all 8 contributors for this article] (2001). Cellular and humoral responses of membrane-bound meningococcal LPS.
• Iversen, Nina; Brandtzæg, Petter & Abildgaard, Ulrich (2001). Consumption of the factor Xa-TFPI complex in meningococcal septicemia.
• Kierulf, Peter; Bjerre, Anna; Brusleto, Berit; Øvstebø, Reidun; Joø, Gun Britt & Rosenqvist, Einar [Show all 9 contributors for this article] (2001). Cellular and humoral responses of membrane-bound meningococcal LPS.
• Deuren, Marcel van & Brandtzæg, Petter (2000). Parents' and GPs' key role in diagnosis of meningococcal septicaemia. The Lancet. ISSN 0140-6736. 356, p. 954–955.
• Bjerre, Anna; Brusleto, Berit; Øvstebø, Reidun; Rosenqvist, Einar; Namork, Ellen & Mollnes, Tom Eirik [Show all 8 contributors for this article] (2000). Cellulære og humorale reaksjoner på membranbundet meningokokk LPS.
• Bjerre, Anna; Brusleto, Berit; Øvstebø, Reidun; Rosenqvist, Einar; Namork, Ellen & Kierulf, Peter [Show all 7 contributors for this article] (2000). Cellebundet endotoxin: er det av betydning?
• Bjerre, Anna; Brusleto, Berit; Øvstebø, Reidun; Rosenqvist, Einar; Namork, Ellen & Kierulf, Peter [Show all 7 contributors for this article] (2000). Cellular responses of membrane-bound meningocccal LPS.
• Bjerre, Anna; Brusleto, Berit; Rosenqvist, Einar; Namork, Ellen; Mollnes, Tom Eirik & Kierulf, Peter [Show all 7 contributors for this article] (2000). Complement activation of membrane-bound meningococcal LPS.
• Bjerre, Anna; Brusleto, Berit; Øvstebø, Reidun; Kierulf, Peter & Brandtzæg, Petter (2000). Is lipid A the principal monocyte activating factor in meningococcal septic shock plasma?
• Bjerre, Anna; Brusleto, Berit; Øvstebø, Reidun; Rosenqvist, Einar; Namork, Ellen & Kierulf, Peter [Show all 7 contributors for this article] (2000). Cellular responses of membrane-bound meningococcal lipopolysaccharides.
• Li, J.J.; Evans, T.; Brandtzæg, Petter & Cohen, J. (1999). Endotoxin blebbing from Neisseria meningitidis as an independent determinant of pathognesis.
• Hellerud, Bernt C & Brandtzæg, Petter (2011). Meningococcal sepsis : beneficial and harmful inflammatory mechanisms. Unipub forlag. ISSN 978-82-8264-141-8.

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