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(Circulation. 2003;107:320.)
© 2003 American Heart Association, Inc.

Basic Science Reports

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

Urs Eriksson, MD; Michael O. Kurrer, MD; Nicole Schmitz; Stephan C. Marsch, MD; Adriano Fontana, MD; Hans-Pietro Eugster, PhD; Manfred Kopf, PhD

From the Department of Internal Medicine (U.E., S.C.M.), University Hospital, Basel; Departments of Pathology (M.O.K.) and Clinical Immunology (A.F., H.-P.E.), University Hospital, Zurich; and Molecular Biomedicine (N.S., M.K.), Swiss Federal Institute of Technology, Zurich, Switzerland.

Correspondence to Urs Eriksson, MD, Medical ICU, University Hospital, Petersgraben 4, Basel CH-4031, Switzerland. E-mail ueriksson{at}uhbs.ch

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 -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.

Key Words: interleukins • myocarditis • cardiomyopathy

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