Published Online
on December 16, 2002

A more recent version of this article appeared on January 21, 2003

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Submitted on July 23, 2002
Revised on September 17, 2002
Accepted on September 18, 2002

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, and 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.

^* To whom correspondence should be addressed. 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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