The granulomatous response in murine Schistosomiasis mansoni does not switch to Th1 in IL-4-deficient C57BL/6 mice
Metwali, A.; Elliott, D.; Blum, A.M.; Li, J.; Sandor, M.; Lynch, R.; Noben-Trauth, N.; Weinstock, J.V.
Journal of Immunology 157(10): 4546-4553
1996
ISSN/ISBN: 0022-1767 PMID: 8906833 Document Number: 455941
Interleukin (IL)-4 plays an important role in polarizing inflammation toward a Th2 response but it is unclear whether IL-4 also serves to prevent expression of Th1 inflammation. Using a genetically pure C57BL/6 IL-4-deficient mouse strain, the role of IL-4 in regulating the production of interferon (IFN)- gamma and Th1 inflammation in granulomas of mice infected with Schistosoma mansoni was investigated. In contrast to normal animals, IL-4 mutant mice generated smaller liver granulomas that contained fewer eosinophils and no mast cells. Collagenase-dispersed granuloma cells were analysed by flow cytometry and cultured in vitro to measure cytokine and immunoglobulin production. Compared with control granuloma cells, IL-4-/- cells secreted only small quantities of IL-5 and IL-10, and expression of the IL-4-dependent molecules IgE and IgG1 as well as B cell surface class II and CD23 was impaired. The granulomas of IL-4 -/- mice produced little IFN- gamma , IgG2a or other molecules associated with Th1 inflammation, even after antigen or anti-CD3 stimulation. Splenocytes from IL-4 -/- mice stimulated with schistosome antigen also failed to produce a Th1 response. The results show that most aspects of the Th2 response in murine schistosomiasis are highly dependent on IL-4 production. In the absence of IL-4, neither the natural local granulomatous response to schistosome ova nor the systemic response to soluble egg antigen switches to the Th1 response. Therefore, the production of IL-4 early in the inflammatory response is not the only factor preventing Th1 expression in inflammation.