Journal
JOURNAL OF IMMUNOLOGY
Volume 166, Issue 10, Pages 6323-6331Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.166.10.6323
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To determine the role of endogenous IL-10 in local antibacterial host defense and in the development of a systemic inflammatory response syndrome during abdominal sepsis, IL-10 gene-deficient (IL-10(-/-)) and wild-type (IL-10(+/+)) mice received an i.p. injection with Escherichia coli. Peritonitis was associated with a bacterial dose-dependent increase in IL-10 concentrations in peritoneal fluid and plasma. The recovery of E. coli from the peritoneal fluid, blood, and lungs was diminished in IL-10(-/-) mice, indicating that endogenous IL-10 impaired bacterial clearance. Despite a lower bacterial load, IL-10(-/-) mice had higher concentrations of TNF, macrophage inflammatory protein-2 and keratinocyte in peritoneal fluid and plasma, and demonstrated more severe multiple organ damage as indicated by clinical chemistry and histopathology. Furthermore, IL-10(-/-) mice showed an increased neutrophil recruitment to the peritoneal cavity. To examine the role of elevated TNF levels in the altered host response in IL-10(-/-) mice, the effect of a neutralizing anti-TNF mAb was determined. Anti-TNF did not influence the clearance of E. coli in either IL-10(+/+) or IL-10(-/-) mice. Furthermore, anti-TNF did not affect leukocyte influx in the peritoneal fluid, multiple organ damage, or survival in IL-10(+/+) mice. In IL-10(-/-) mice, anti-TNF partially attenuated neutrophil recruitment and multiple organ damage, and prevented the increased lethality. These data suggest that although endogenous IL-10 facilitates the outgrowth and dissemination of bacteria during E. coli peritonitis, it protects mice from lethality by attenuating the development of a systemic inflammatory response syndrome by a mechanism that involves inhibition of TNF release.
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