Interleukin-4 and Interleukin-10 Are Involved in Host Resistance toStaphylococcus aureusInfection through Regulation of Gamma Interferon

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Abstract
Our previous study showed that gamma interferon (IFN-γ), a T-helper 1 (Th1)-type cytokine, plays a detrimental role inStaphylococcus aureusinfection in mice. In this study, the role of Th2-type cytokines such as interleukin-4 (IL-4) and IL-10 inS. aureusinfection was investigated. IL-10 mRNA was induced in parallel with IFN-γ in the spleens and kidneys of mice duringS. aureusinfection, whereas IL-4 mRNA was induced in the spleens but not in the kidneys of these animals. Spleen cells obtained fromS. aureus-infected mice produced lower titers of IFN-γ and higher titers of IL-4 and IL-10 in response to heat-killedS. aureusthan did those from uninfected mice. Administration of anti-IL-4 monoclonal antibody (MAb) or anti-IL-10 MAb inhibited the elimination ofS. aureuscells from the kidneys of mice. IFN-γ mRNA expression was enhanced in the spleens of anti-IL-4 MAb- or anti-IL-10 MAb-treated mice and also in the kidneys of anti-IL-4 MAb-treated animals. Next, we evaluated the role of IFN-γ inS. aureusinfection in IFN-γ−/−mice. An increase in survival rates, a decrease in bacterial numbers in the kidneys, and an amelioration of histologic abnormalities in these organs were observed in IFN-γ−/−mice compared with those in IFN-γ+/+mice. Administration of MAb against IL-4 or IL-10 failed to affect bacterial growth in the spleens and kidneys of IFN-γ−/−mice irrespective of the expression of Th2 response. These results suggest thatS. aureusinfection induced a Th2 response and that IL-4 and IL-10 might play a protective role through the regulation of IFN-γ inS. aureusinfection.