Different cytokines profiles in spleen cells and liver granuloma of Schistosoma mansoni experimentally infected mice during disease development.

To determine the importance of Th1 and Th2 cells in modulating granuloma formation, mRNA transcripts for Th1 (IL-2 and IFN-gamma) and Th2 (IL-4 and IL-5) cytokines were assessed by the molecular technique of in situ hybridization in the liver granuloma. The molecular studies showed few number of cells expressing mRNA transcripts for INF-gamma whereas, considerable number of IL-2 cells were present in the liver granuloma at 6 weeks post-infection (p.i.). Complete disappearance of IFN-gamma expressing cells were found when the disease progressed to 13 weeks p.i. Conversely, very high number of cells expressing mRNA transcripts for IL-4 and fair number of IL-5 cells were present at 7 weeks p.i. with a peak level of IL-4 cells at 13 weeks p.i. These in situ molecular studies of the liver tissues, demonstrated that Th1 cells were present at the very early granuloma development. Moreover, Th2 cells were required for its full development. The main interesting finding was the number of cells expressing mRNA for IL-4, as they were very huge and it might exceed the total number of lymphocytes per se in the granuloma. Lymphocytes from experimentally infected mice-spleen cells were also cultured in vitro with S. mansoni soluble egg antigen (SEA) and the same cytokines of lymphocyte supernatant were measured by ELISA assay. The levels of IFN-gamma and IL-2 were high to 6 wk. p.i. with a slight decline of IFN-gamma, and increasing amount of IL-2 at 10-13 wk p.i. Spleen lymphocytes of fully formed granuloma secreted high levels of IL-4 and IL-5. The results suggest that the development of schistosome egg-induced liver granuloma is a complex process and both Th1 and Th2 cell subsets sharing with other inflammatory cells (non lymphocytes), may play an important role in regulating and modulating the immuno-pathology of granuloma formation and the subsequent hepatic fibrosis.