CYTOKINE REGULATION OF PATHOLOGY IN SCHISTOSOMIASIS

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Our long-term goal is to understand the immunologic mechanisms that account for the egg-induced pathology and its modulation with chronic schistosomiasis. Intense study of the granulomatous responses in murine models and has produced a complicated picture of a dynamic T cell- dependent reaction in which cytokines coordinate the influx of effector cells to the granuloma. IL-2, IL-4, IL-10, and TNFalpha appear to play key roles in the induction and regulation of the granuloma. Whether these observations pertain to human disease is unknown. Because controlled and invasive studies in humans would be impossible, extension of these observations to a non human primates model that closely resemble human disease is of particular value. The present study proposes a series of experiments to determine the role and sequential expression of T cell derived cytokines have in the induction and modulation of egg-induced pathology in the baboon. Individual animals will undergo multiple serial biopsies of the spleen, liver, and bladder during the inductive, maintenance and modulatory phases of the granulomatous inflammation. These studies will correlate Th1 vs Th2 responses generated in the peripheral blood and spleen with the pattern of local cytokine responses produced in egg-induced granulomas. Additional animals will subsequently be administered recombinant human IL-12 or IL-4 at different periods during the acute infection to examine the role these cytokines have in altering the pattern of granuloma formation. Finally, the effects of curative chemotherapy on the subsequent granulomatous responses with re-infection will be examined. Because comparatively little is known about immune regulation of the granuloma in S, haematobium infections, studies will examine infection with this parasite as well as S. mansoni.