IL-6-deficient mice form granulomas in murine schistosomiasis that exhibit an altered B cell response

Abstract

IL-6 can play an important role in various biological activities. Using IL-6-deficient, 129 x C57BL/6 mice and normal littermate controls, we studied the role of IL-6 in granulomas of mice infected with schistosomiasis mansoni. Granulomas from IL-6(+/+) mice produced large quantities of IL-6, derived from T, B, and myeloid cells. Yet, IL-6 mutant mice generated normal-appearing granulomas of appropriate size. Multiple-parameter flow cytometric analysis of dispersed granuloma cells revealed no substantial differences. Granuloma cells and splenocytes were cultured in vitro to measure cytokine and immunoglobulin production. Compared to control cells, IL-6(-/-) granuloma cells secreted more IL-4, IL-5, and IL-10. However, splenocytes secreted cytokines comparably. In the IL-6(-/-) state, the granuloma cells released less IgE and substantially more IgM, although IgG1, IgG2a, and IgA secretion remained normal. ELISPOT assay showed that dispersed granuloma cells from IL-6-deficient animals had substantially more IgM-secreting B cells. Thus, schistosome granulomas make IL-6 that is not essential for most aspects of granuloma development. However, IL-6 deficiency results in some disturbance of granuloma cytokine and immunoglobulin expression.