Interleukin-6–Deficient Mice Resist Development of Autoimmune Myocarditis Associated With Impaired Upregulation of Complement C3

Abstract

Background— Interleukin (IL)-6 regulates various aspects of the immune response. In the context of heart diseases, it has been recognized as a prognostic factor for dilated cardiomyopathy, which often results from myocarditis. Methods and Results— Using IL-6–deficient mice, we studied the role of IL-6 in a model of autoimmune myocarditis resulting from immunization with a peptide derived from cardiac α-myosin. Prevalence and severity of myocarditis were markedly reduced in the absence of IL-6. CD4 + T cells from immunized IL-6–deficient mice proliferated poorly on restimulation with specific antigen in vitro and did not mediate disease on adoptive transfer into IL-6–competent RAG-2–deficient mice, which otherwise lack B cells and T cells. Production of complement C3, a crucial factor for the development of myocarditis, was strongly upregulated in IL-6 +/+ but not in IL-6–deficient mice after immunization. Conclusions— Our results demonstrate that IL-6 is required for the expansion of autoimmune CD4 + T cells and the pathogenesis of autoimmune myocarditis, possibly by upregulation of complement C3.