title: Massive Organ Inflammation in Experimental and in Clinical Meningococcal Septic Shock.
abstract: 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)-1β, 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.
authors.affiliation: *Department of Pediatrics, Oslo University Hospital Ullevål, and University of Oslo, Oslo †Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo ‡Department of Immunology, K.G. Jebsen IRC, University of Oslo, Oslo §Department of Medical Biochemistry, Oslo University Hospital Ullevål, and University of Oslo, Oslo ||Department of Anesthesiology, Nordland Hospital, and University of Nordland, Bodø ¶Department of Anesthesiology, University of Tromsø, Tromso #Department of Medical Biochemistry, Stavanger University Hospital, Stavanger **Department of Research and Development in Forensic Pathology, The Norwegian Institute of Public Health, Oslo ††Research Laboratory, Nordland Hospital, Bodø ‡‡Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, Tromso §§Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim ||||Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Bernt C
authors.initials: BC
authors.lastname: Hellerud
authors.forename: Ole K
authors.initials: OK
authors.lastname: Olstad
authors.forename: Erik W
authors.initials: EW
authors.lastname: Nielsen
authors.forename: Anne-Marie S
authors.initials: AM
authors.lastname: Trøseid
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Skadberg
authors.forename: Ebbe B
authors.initials: EB
authors.lastname: Thorgersen
authors.forename: Åshild
authors.initials: Å
authors.lastname: Vege
authors.forename: Tom E
authors.initials: TE
authors.lastname: Mollnes
authors.forename: Petter
authors.initials: P
authors.lastname: Brandtzæg
mesh_terms: D000293:Adolescent; D000818:Animals; D001779:Blood Coagulation Factors / Q000096:biosynthesis / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D008589:Meningococcal Infections / Q000235:genetics / Q000378:metabolism*; D009345:Neisseria meningitidis / Q000302:isolation & purification; D012772:Shock, Septic / Q000235:genetics / Q000378:metabolism*; D034421:Sus scrofa; D014158:Transcription, Genetic
chemical_list: D001779:Blood Coagulation Factors; D015815:Cell Adhesion Molecules; D016207:Cytokines