ENDOGENOUS IL-10 REGULATES IFN-GAMMA AND IL-5 CYTOKINE PRODUCTION ANDTHE GRANULOMATOUS RESPONSE IN SCHISTOSOMIASIS MANSONI-INFECTED MICE

In murine Schistosomiasis mansoni circumovum, granuloma formation is r egulated by pro- and anti-inflammatory cytokines. Among the latter, in terleukin-10 (IL-10) has been shown to regulate the inflammatory respo nse. In this study we examined the role of endogenously produced IL-10 in T-helper 1 (Th1)- and Th2-type cytokine production and granuloma f ormation. The dynamics of IL-10 production through the course of the i nfection were different in granuloma versus splenic cells. In the form er, production peaked during the early developmental stage (6 weeks of infection) of the granuloma and then declined. In splenocytes product ion peaked at 12 weeks, before downmodulation of the granuloma respons e. In the developing granuloma both macrophages and T cells secreted I L-10. In anti-IL-10 monoclonal antibody (mAb)-supplemented granuloma c ell cultures endogenous IL-10-mediated regulation of interferon-gamma (IFN-gamma) was manifest only at 6 weeks; that of IL-2 continued throu ghout the infection (6-20 weeks). IL-4 production was unaffected, but IL-5 production was regulated at the 6 and 8 weeks time point. Splenoc ytes showed regulation of IFN-gamma and IL-2 production at the peak of the granulomatous response (8 weeks). IL-4 production was not regulat ed, whereas IL-5 production was regulated only at 6 weeks. Repeated in jections of anti-IL-10 mAb given to mice at 6, 12 or 20 weeks of the i nfection significantly enhanced liver and lung granuloma growth, tissu e eosinophilia, and IFN-gamma, IL-5 production at the early developmen tal phase (6 weeks) of the lesions. Thus, in schistosome-infected mice endogenous IL-10 is shown to regulate Th1- and Th2-type cytokine prod uction and granuloma formation during the early Th0/Th1 phase of the i mmune response.