beta 2-Adrenergic agonists suppress rat autoimmune myocarditis potential role of beta 2-adrenergic stimulants as new therapeutic agents for myocarditis

Article

关键词: NECROSIS-FACTOR-ALPHA;    T-CELLS;    IN-VIVO;    MYOSIN;    INTERLEUKIN-10;    RECEPTOR;    HEART;    MICE;    RNA;    CARDIOMYOPATHY;   

DOI  :  10.1161/CIRCULATIONAHA.105.607903

来源: SCIE

【 摘 要 】

Background-The therapeutic potential of beta 2-adrenergic receptor (AR) agonists in the treatment of autoimmune diseases has been reported. However, the role of these drugs in the myocardial structure-induced autoimmune process, which is thought to play a crucial role in the progression of myocarditis to subsequent complications, has not been elucidated. Methods and Results-Experimental autoimmune myocarditis (EAM) was induced in rats by immunization with cardiac myosin. On daily administration from day 0 after immunization, the beta 2-selective AR agonists formoterol or salbutamol ameliorated EAM on day 21 and increased myocardial interleukin-10/interferon-gamma mRNA levels. Propranolol, a nonselective beta-AR antagonist, aggravated EAM on day 21 and decreased mRNA levels, whereas metoprolol, a beta 1-selective AR antagonist, showed no effect. These results were reflected in vivo by the proliferation of cardiac myosin-primed lymph node cells from drug-treated rats. In vitro addition of beta 2-selective AR agonists inhibited the activation of cardiac myosin fragment-specific myocarditogenic T lymphocytes, and this effect was reversed by ICI118,551, a beta 2-selective AR antagonist. Furthermore, treatment with 2 different beta 2-selective AR agonists starting on day 14 also ameliorated EAM on day 21. Conclusions-beta 2-AR stimulation suppressed the development of EAM by inhibiting cardiac myosin-specific T-lymphocyte activation in lymphoid organs and by shifting the imbalance in Th1/Th2 cytokine toward Th2 cytokine. Furthermore, it also ameliorated established myocardial inflammation. beta 2-AR-stimulating agents may represent important immunomodulators of the cardiac myosin-induced autoimmune process and have potential as a new therapy for myocarditis.

【 授权许可】

Free