We have previously demonstrated the protective role of interleukin (IL)-6 against septic lung injury induced by lipopolysaccharide (LPS) using IL-6 knock-out (−/−) mice. This protection is mediated, at least partly, through the inhibition of the enhanced local expression of proinflammatory cytokines. In the present study, we addressed whether IL-6 regulates oxidative stress in the lung generated by LPS exposure using IL-6 (−/−) and corresponding wild type (WT) mice. Intraperitoneal LPS (1 mg/kg) challenge induced transcriptional expressions of inducible nitric oxide synthase and heme oxygenase −1 in the lung of mice with both genotypes. In the presence of LPS, these expressions were significantly greater in IL-6 (−/−) than in WT mice. Immunohistochemistry also showed that LPS induced a significant increase in 8-hydroxy-2′-deoxyguanosine formation in the lung as compared to vehicle. Furthermore, the formation was more intense in IL-6 (−/−) than in WT mice in the presence of LPS challenge. In the presence of LPS, lipid peroxidation in the lung was significantly greater in IL-6 (−/−) than in WT mice. These data suggest that the possible mechanisms in which endogenous IL-6 protects against septic lung injury induced by LPS involve, at least in part, its antioxidative properties.
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