Interleukin-10 impairs host defense in murine pneumococcal pneumonia

The effects of recombinant interleukin (IL)-10 and the role of endogenous IL-10 were determined in C57B1/6 mice with pneumonia induced by intranasal inoculation with 10(6) cfu of Streptococcus pneumoniae. Pneumonia induced sustained expression of IL-10 mRNA and protein in lungs, but IL-10 remained undetectable in plasma. Intranasal inoculation of S. pneumoniae in combination with IL-10 (1500 U/mouse) resulted in decreased lung concentrations of tumor necrosis factor-alpha (TNF) and interferon (IFN)-gamma, increased bacterial counts in lungs and blood, and early lethality. Conversely, pretreatment (-2 h) of mice with an anti-IL-10 monoclonal antibody (2 mg/mouse) was associated with increased lung levels of TNF and IFN-gamma, reduced bacterial counts in lungs and plasma 40 h after the inoculation, and prolonged survival. These results indicate that during pneumococcal pneumonia, IL-10 attenuates the proinflammatory cytokine response within the lungs, hampers effective clearance of the infection, and shortens survival.