MASSIVE ORGAN INFLAMMATION IN EXPERIMENTAL AND IN CLINICAL MENINGOCOCCAL SEPTIC SHOCK

作者：Hellerud Bernt C^*; Olstad Ole K; Nielsen Erik W; Troseid Anne Marie S; Skadberg Oyvind; Thorgersen Ebbe B; Vege Ashild; Mollnes Tom E; Brandtzaeg Petter

来源：Shock, 2015, 44(5): 458-469.

DOI：10.1097/SHK.0000000000000441

• Chemokines
• coagulation
• cytokines
• endotoxin
• immune response
• Neisseria meningitidis
• sepsis
• Streptococcus pneumoniae
• sudden infant death syndrome

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, 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.

• 出版日期2015-11