Lymphokine regulation of granuloma formation in murine schistosomiasis mansoni

The pathology in schistosomiasis mansoni is primarily due to hepatic and intestinal granuloma formation around deposited eggs and subsequent fibrosis. The intensity of the granulomatous response is dependent on the lymphokines produced by T cells in response to soluble egg antigens (SEA). The present study examined the relationship of three inflammatory lymphokines, IL-2, IL-4, and IFN-gamma in granuloma formation during the acute stage of the murine infection. Repeated injections of anti-IL-2 or anti-IL-4 mAbs in vivo significantly diminished pulmonary granuloma formation in infected mice and demonstrated that both IL-2 and IL-4 were involved during the period of peak granuloma formation. Administration of anti-IL-2 mAb decreased IL-2, but not IL-4 production, while anti-IL-4 mAb treatment decreased both IL-2 and IL-4 production by splenic T cells. Administration of anti-IFN-gamma mAb to infected mice significantly increased pulmonary granuloma formation and increased the production of both IL-2 and IL-4 by splenic T cells. Repeated injections of graded doses of recombinant IFN-gamma given to mice between 6 and 8 weeks of infection decreased pulmonary granuloma formation as well as IL-2 and IL-4 production by splenic T cells. These data demonstrate that the regulation of lymphokines, IFN-gamma, IL-2, and IL-4, is important in influencing the intensity of granuloma formation. IL-2 and IL-4 appear to play a proinflammatory role in granuloma formation, while IFN-gamma may downregulate splenic IL-2 and IL-4 production and, more importantly, the corresponding inflammatory granuloma formation.