The effect of the membrane attack complex and TNF-alpha on the developmentof organ damage induced by leukocytes during sepsis

Background: The synergism between TNF-alpha and the MAC (C5b - C9) on the e ndothelial expression of ICAM-1 and P-selectin was investigated in an endot oxin-induced septic shock animal model. Methods: In C6 deficient PVG (C-) and congenic PVG (C+) rats with normal he molytic complement activity, septic shock was induced via intraperitoneal. injection of lipopolysaccacharid (LPS) in doses from 0.5 up to 20 mg/kg bod yweight (BW). Lung tissue was harvested 4, 8, and 12 hours post injection a nd investigated by immunhistochemistry and PCR technique for the protein an d molecular expression of adhesion molecules ICAM-1 and P-selectin and RNas e protection assay for the mRNA-level of the cytokines IL-alpha, IL-1 beta, IL-6 and TNF-alpha. Results: An induction of P-selectin as well as infiltration of MAC-1(+) cel ls was demons:rated by immunhistochemistry in all LPS treated groups. The i nduction of P-selectin was reduced 12 hrs after LPS-injection (5 mg/kg BW) in PVG (C -) versus PVG (C--) rats, but without statistical significance (n = 5). The PCR analysis demonstrated variable induction of adhesion molecul es and cytokines after LPS injection, without significant difference betwee n PVG (C-) and PVG (C+) rats. Conclusion: In vitro results demonstrating a synergism between MAC and TNF- alpha, on the endothelial expression of adhesion molecules in septic shock could not be confirmed using this model.