Endogenous IL-10 regulates IFN-gamma and IL-5 cytokine production and the granulomatous response in Schistosomiasis mansoni-infected mice

Abstract

In murine Schistosomiasis mansoni circumovum, granuloma formation is regulated by pro- and anti-inflammatory cytokines. Among the latter, interleukin-10 (IL-10) has been shown to regulate the inflammatory response. In this study we examined the role of endogenously produced IL-10 in T-helper 1 (Th1)- and Th2-type cytokine production and granuloma formation. The dynamics of IL-10 production through the course of the infection were different in granuloma versus splenic cells. In the former, production peaked during the early developmental stage (6 weeks of infection) of the granuloma and then declined. In splenocytes production peaked at 12 weeks, before down-modulation of the granuloma response. In the developing granuloma both macrophages and T cells secreted IL-10. In anti-IL-10 monoclonal antibody (mAb)-supplemented granuloma cell cultures endogenous IL-10-mediated regulation of interferon-gamma (IFN-gamma) was manifest only at 6 weeks; that of IL-2 continued throughout the infection (6-20 weeks). IL-4 production was unaffected, but IL-5 production was regulated at the 6 and 8 weeks time point. Splenocytes showed regulation of IFN-gamma and IL-2 production at the peak of the granulomatous response (8 weeks). IL-4 production was not regulated, whereas IL-5 production was regulated only at 6 weeks. Repeated injections of anti-IL-10 mAb given to mice at 6, 12 or 20 weeks of the infection significantly enhanced liver and lung granuloma growth, tissue eosinophilia, and IFN-gamma, IL-5 production at the early developmental phase (6 weeks) of the lesions. Thus, in schistosome-infected mice endogenous IL-10 is shown to regulate Th1- and Th2-type cytokine production and granuloma formation during the early Th0/Th1 phase of the immune response.