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 alpha-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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Autoantibodies / blood
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Autoimmune Diseases / complications
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Autoimmune Diseases / immunology
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Autoimmune Diseases / pathology
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Autoimmune Diseases / prevention & control*
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B-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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Cell Division / immunology
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Cells, Cultured
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Complement C3 / metabolism*
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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Disease Models, Animal
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Disease Susceptibility / immunology
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Immunization
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Immunohistochemistry
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Interleukin-6 / deficiency*
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Interleukin-6 / genetics
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Interleukin-6 / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Myocarditis / complications
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Myocarditis / immunology
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Myocarditis / pathology
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Myocarditis / prevention & control*
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Myocardium / immunology
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Myocardium / pathology
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Peptide Fragments / immunology
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Tumor Necrosis Factor-alpha / immunology
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Up-Regulation
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Ventricular Myosins / immunology
Substances
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Autoantibodies
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Complement C3
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DNA-Binding Proteins
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Interleukin-6
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Peptide Fragments
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Rag2 protein, mouse
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Tumor Necrosis Factor-alpha
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V(D)J recombination activating protein 2
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Ventricular Myosins