Interleukin-4 and interleukin-10 are involved in host resistance to Staphylococcus aureus infection through regulation of gamma interferon

Our precious study showed that gamma interferon (IFN-gamma), a T-helper 1 ( Th1)-type cytokine, plays a detrimental role in Staphylococcus aureus infec tion in mice. In this study, the role of Th2-type cytokines such as interle ukin-4 (IL-4) and IL-10 in S. aureus infection was investigated. IL-10 mRNA was induced in parallel with IFN-gamma in the spleens and kidneys of mice during S. aureus infection, whereas IL-4 mRNA was induced in the spleens bu t not in the kidneys of these animals. Spleen cells obtained from S. aureus -infected mice produced lower titers of IFN-gamma and higher titers of IL-4 and IL-10 in response to heat-killed S. aureus than did those from uninfec ted mice. Administration of anti-IL-4 monoclonal antibody (MAb) or anti-IL- 10 MAb inhibited the elimination of S. aureus cells from the kidneys of mic e. IFN-gamma 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-tre ated animals. Next, we evaluated the role of IFN-gamma in S. aureus infecti on in TFN-gamma(-/-) mice. An increase in survival rates, a decrease in bac terial numbers in the kidneys, and an amelioration of histologic abnormalit ies in these organs were observed in IFN-gamma(-/-) mice compared with thos e in IFN-gamma(-/-) mice. Administration of MAb against IL-4 or IL-10 faile d to affect bacterial growth in the spleens and kidneys of IFN-gamma(-/-) m ice irrespective of the expression of Th2 response. These results suggest t hat S. arn eus infection induced a Th2 response and that IL-4 and IL-10 mig ht play a protective role through the regulation of IFN-gamma in S. aureus infection.