The role of interferon-γ in the pathogenesis of acute intra-abdominal sepsis.

Abstract

Several studies indicate that IFN-&#x3b3; facilitates systemic inflammation during endotoxin-induced shock. However, the pathobiology of IFN-&#x3b3; in clinically relevant models of septic shock, such as CLP, is not well understood. In this study, the role of IFN-&#x3b3; in the pathogenesis of CLP-induced septic shock was evaluated by examining IFN-&#x3b3; production at the tissue and cellular levels. The impact of IFN-&#x3b3; neutralization on systemic inflammation, bacterial clearance, and survival was also determined. Following CLP, concentrations of IFN-&#x3b3; in plasma and peritoneal lavage fluid were low in comparison with concentrations of IL-6 and MIP-2, as was IFN-&#x3b3; mRNA expression in liver and spleen. The overall percentage of IFN-&#x3b3;+ splenocytes was <5% after CLP and not statistically different from control mice. Intracellular IFN-&#x3b3; was present in a large proportion of peritoneal exudate cells after CLP, primarily in infiltrating myeloid cells and NK cells. i.p. myeloid cell activation was decreased in IFN-&#x3b3;KO mice, and plasma concentrations of IL-6 and MIP-2 were significantly lower in IFN-&#x3b3;KO mice and in mice treated with anti-IFN-&#x3b3; compared with controls, but bacterial clearance was not affected. IFN-&#x3b3;KO mice were resistant to CLP-induced mortality when treated with systemic antibiotics. However, neutralization of IFN-&#x3b3; with blocking antibodies did not improve survival significantly. These studies show that IFN-&#x3b3; facilitates the proinflammatory response during CLP-induced septic shock. However, neutralization of IFN-&#x3b3; did not improve survival uniformly.