SCHISTOSOMA-MANSONI IN IL-4-DEFICIENT MICE

Immunopathology and immune responses to Schistosoma mansoni were exami ned in IL-4 -/- mice. IL-5 and IL-10 production by lymphoid cells stim ulated with soluble egg antigen (SEA), peripheral eosinophilia and ser um levels of soluble IL-4 receptor but not IgE were all significantly elevated over background normal levels in IL-4 -/- mice as a result of infection. Additionally, IL-10 and IL-5 in addition to IL-2 and IFN-g amma-transcripts were equally evident in diseased liver tissue from in fected IL-4 -/- and wild-type mice. Nevertheless, analysis of antigen- stimulated IL-2, IL-4, IL-5, IL-10 and IFN-gamma production by lymphoi d organ cells from infected or egg-injected IL-4 -/- mice revealed a m ore T(h)1-like pattern of cytokine production (IFN-gamma > IL-5) than in (wild-type) mice in which a stronger type 2 response to SEA was det ectable (IL-4, IL-5 > IFN-gamma). Despite this, at 8 and 16 weeks afte r infection, liver pathology, as indicated by the size, cellularity, c ellular composition and collagen content of granulomas, was similar in IL-4 -/- and wild-type animals, As in wild-type animals, granuloma si ze at week 16 was smaller than at week 8, indicating that modulation h ad occurred in the absence of IL-4. Differences in pathology were seen only when eggs were experimentally embolized to the lungs, in which c ase IL-4 -/- mice made smaller granulomatous responses than did wild-t ype animals. These data clearly show that IL-4 is not necessary for th e hepatic granuloma formation which occurs during experimental schisto somiasis.