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

Authors: Afanasyeva, M; Wang, Y; Kaya, Z; Park, S; Zilliox, M J; Schofield, B H; Hill, S L; Rose, N R

Published In Am J Pathol, (2001 Jul)

Abstract: 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)-gamma production in vitro. Based on the latter finding, we hypothesized that IFN-gamma limits disease. Indeed, IFN-gamma blockade with a mAb exacerbated disease. The ameliorating effect of IL-4 blockade was abrogated by co-administration of anti-IFN-gamma 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-gamma limits it. Suppression of IFN-gamma represents at least one of the mechanisms by which IL-4 promotes EAM.

PubMed ID: 11438466 Exiting the NIEHS site

MeSH Terms: Animals; Antibodies, Monoclonal/pharmacology; Autoantibodies/analysis; Autoimmune Diseases/immunology; Autoimmune Diseases/pathology*; Autoimmune Diseases/physiopathology*; Cells, Cultured; Cytokines/biosynthesis; Immunoglobulin E/analysis; Immunoglobulin G/analysis; Interferon-gamma/immunology; Interleukin-4/immunology; Interleukin-4/physiology*; Mice; Mice, Inbred Strains; Myocarditis/immunology; Myocarditis/pathology*; Myocarditis/physiopathology*; Myocardium/metabolism; Myocardium/pathology; Myosins/immunology; Myosins/metabolism; Phenotype; Severity of Illness Index; Spleen/metabolism; Spleen/pathology; Th2 Cells/pathology*

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