Endogenous IL-10 leads to impaired bacterial clearance and reduced survival in a murine model of chronic peritonitis.

Abstract

We previously observed insufficient neutrophil accumulation and a lack of TNF-alpha response at the site of infection until bacteria numbers >10(5) colony forming units in our model of chronic murine peritonitis, suggesting a defective host response after bacterial challenge with Klebsiella pneumoniae (Klebsiella). The aim of this study was to determine a potentially immunosuppressive effect of IL-10 in this model of chronic peritonitis. Balb/c animals were injected with 10(3) colony forming units Klebsiella intraperitoneally. Gentamicin (5 mg/kg/day BID) was given subcutaneously (s.c.) for two days and then withdrawn. Animals were treated with anti-IL-10 antibody or IgG isotype control (s.c.) before or after Klebsiella administration. Survival was determined over 14 days. Similarly treated animals were harvested after 48 h to obtain liver tissue, peritoneal fluid and blood. Bacteria and neutrophil counts were determined. TNF-alpha and IL-10 were measured by ELISA. Anti-IL-10 antibody significantly increased survival and bacterial clearance in the observed compartments. Anti-IL-10 administration did not lead to an increase in TNF-alpha concentrations or neutrophil accumulation at the site of infection at lower levels of Klebsiella. We conclude that endogenous IL-10 is detrimental for survival and bacterial clearance in this model of chronic peritonitis.