Myocardial dysfunction in an experimental model of autoimmune myocarditis: role of IFN-gamma.
Experimental autoimmune myocarditis obtained in mice by immunization with heart antigens is characterized by the presence of lymphomononuclear infiltrates in atria and ventricles. Here we show the ability of soluble factors released by immune cells from mice immunized with heart antigens to decrease heart contractility in a similar way to a muscarinic agonist. These effects appear to be mediated by IFN-gamma since all of them could be blocked by an anti-IFN-gamma monoclonal antibody. Moreover, the negative inotropic effect induced by immune cell-conditioned media was blocked by atropine, confirming previous findings that IFN acts as a muscarinic agonist on isolated atria. The role of locally released cytokines and especially of IFN-gamma was also evaluated in infiltrated autoimmune myocarditis hearts; thus, the addition of monoclonal anti-IFN-gamma antibody reversed the decreased contractility characteristics of this model. We conclude that IFN released both systemically and locally by autoreactive T cells may contribute to the impaired cardiac function in this experimental model of autoimmune myocarditis.
Pérez Leirós
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C
Centro de Estudios Farmacológicos y Botánicos (CEFYBO)-CONICET y Cátedra de Farmacología, Facultad de Odontología, Universidad de Buenos Aires, Argentina. cali@cefybo.edu.ar
Goren
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N
Sterin-Borda
L
L
Borda
E S
ES
D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology*; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects / Q000276:immunology; D009205:Myocarditis / Q000276:immunology*; D009206:Myocardium / Q000276:immunology; D011976:Receptors, Muscarinic / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
D017077:Culture Media, Conditioned; D011976:Receptors, Muscarinic; D007371:Interferon-gamma