Microbiological and inflammatory effects of murine recombinant interleukin-10 in two models of polymicrobial peritonitis in rats

Abstract

A protective effect of interleukin-10 (IL-10) against the development of lethal shock has been demonstrated in various animal models. In contrast, the immunosuppressant properties of this mediator have been minimally evaluated in low-mortality models of infections. The clinical, microbiological, and inflammatory effects of murine recombinant IL-10 (mrIL-10) therapy were evaluated in two models of peritonitis in rats, which differed in the degree of severity of peritoneal inflammation 3 days after inoculation of Escherichia coli and Bacteroides fragilis with or without Enterococcus faecalis. The severity of the disease remained unchanged compared to that in control animals. A dose-related decrease in the peritoneal phagocyte count was observed in the treated groups compared to the counts in control animals. The subsequent experiments were performed exclusively in the mixed gram-positive-gram negative model, which exhibits an intense and prolonged inflammatory response with similar criteria. The early effects of mrIL-10 (evaluated 6 h after inoculation), repeated injections of mrIL-10 (four doses injected from 0 to 9 h after bacterial challenge), and pretreatment (two doses injected 6 and 3 h before inoculation) were evaluated. The clinical and microbiological parameters remained unchanged in the treated animals. Decreases in the peritoneal phagocyte count and the peritoneal concentration of tumor necrosis factor were observed following repeated injections of mrIL-10. In summary, our data suggest that mrIL-10 does not worsen the manifestations of sepsis. However, these results need to be confirmed in clinical practice.

FIG. 1

Plasma mrIL-10 concentrations measured after intramuscular injection of 125, 250, or 500 μg of mrIL-10/kg, assayed in groups of five animals. The results are expressed as means ± SDs.

FIG. 2

Phagocyte counts (A) and concentrations of TNF (B) and IL-6 (C) in peritoneal fluid on day 3 in uninfected animals (model I) and infected animals (models II and III) receiving either placebo or mrIL-10 at a dose of 125 or 250 μg/kg injected intramuscularly at the time of bacterial challenge. The results are expressed as means + SDs (10 animals in each group). ∗, P < 0.05 compared to placebo.

FIG. 3

TNF (A), IL-6 (B), and IL-10 (C) concentrations in plasma (open bars) and peritoneal fluid (solid bars) collected 6 h after bacterial challenge in five groups of five infected animals receiving, at the time of bacterial challenge, an intramuscular injection of placebo; a dose of 125, 250, or 500 μg of mrIL-10/kg; or a dose of 125 μg/kg repeated 3 h after inoculation (2× 125). The results are expressed as means + SDs.

FIG. 4

Phagocyte counts (A) and concentrations of TNF (B) and IL-6 (C) in peritoneal fluid collected on day 3 in three groups of five infected animals receiving four doses of either placebo or 250 or 500 μg of mrIL-10/kg injected intramuscularly between the time of bacterial challenge and the ninth hour of the study. The results are expressed as means + SDs. ∗, P < 0.05 compared to placebo.