IL-10 IMPROVES LUNG INJURY AND SURVIVAL IN PSEUDOMONAS-AERUGINOSA PNEUMONIA

Pseudomonas aeruginosa is the most frequent Gram-negative pathogen cau sing nosocomial pneumonia. Four different strains of P. aeruginosa (in cluding three isogenic transposon mutants) were utilized in experiment s in mice to characterize the specific patterns of cytokine generation in response to bacterial products and cytotoxicity. Intratracheal ins tillation of any of the strains led to the up-regulation of IL-1 beta, IL-6, and TNF-alpha mRNA. Instillation of the cytotoxic strains (PA10 3, PA103tox::Omega) led to IL-l ii mRNA up-regulation in the lungs and increased concentrations of IL-10 in the blood. In contrast, the inst illation of the noncytotoxic strains (PA01, PA103exsA::Omega) did not lead to an increase in IL-10 mRNA in the lungs or to an increase of IL -10 concentration in blood. IL-10 production appears to be a response to either cellular injury or to specific cytotoxic exoproducts produce d by the bacteria. The systemic administration of rIL-10 significantly decreased the lung injury and the mortality in mice who had received the cytotoxic strains. The improvement in survival induced by administ ration of rIL-10 required the concomitant presence of IFN-gamma, as bl ockade of IFN-gamma with a neutralizing Ab led to 100% mortality, desp ite the administration of rIL-10. These results suggest that IL-10 is produced in response to specific bacterial products and that there is a potential role for IL-10 in the treatment of cytotoxic P. aeruginosa pneumonia.