Experimental autoimmune myocarditis in A/J mice is an interleukin-4-dependent disease with a Th2 phenotype

Marina Afanasyeva, Yan Wang, Ziya Kaya, Sung Park, Michael J. Zilliox, Brian H. Schofield, Susan L. Hill, Noel R. Rose

Research output: Contribution to journalArticlepeer-review


Myocarditis in humans is often associated with an autoimmune process in which cardiac myosin (CM) is a major autoantigen. Experimental autoimmune myocarditis (EAM) is induced in mice by immunization with CM. We found that EAM in A/J mice exhibits a Th2-like phenotype demonstrated by the histological picture of the heart lesions (eosinophils and giant cells) and by the humoral response (association of IgG1 response with disease and up-regulation of total IgE). Blocking interleukin (IL)-4 with anti-IL-4 monoclonal antibody (mAb) reduced the severity of EAM. This reduction in severity was associated with a shift from a Th2-like to a Th1-like phenotype represented by a reduction in CM-specific IgG1; an increase in CM-specific IgG2a; an abrogation of total IgE response; a decrease in IL-4, IL-5, and IL-13; as well as a dramatic increase in interferon (IFN)-γ production in vitro. Based on the latter finding, we hypothesized that IFN-γ limits disease. Indeed, IFN-γ blockade with a mAb exacerbated disease. The ameliorating effect of IL-4 blockade was abrogated by co-administration of anti-IFN-γ mAb. Thus, EAM represents a model of an organ-specific autoimmune disease associated with a Th2 phenotype, in which IL-4 promotes the disease and IFN-γ limits it. Suppression of IFN-γ represents at least one of the mechanisms by which IL-4 promotes EAM.

Original languageEnglish (US)
Pages (from-to)193-203
Number of pages11
JournalAmerican Journal of Pathology
Issue number1
StatePublished - Jul 2001
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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