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 × 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 culturedin vitroto 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.