Beta2-selective AR agonists (formoterol or salbutamol) ameliorated experimental autoimmune myocarditis in rats on day 21 and increased myocardial IL-10/IFN-gamma mRNA levels.
Does beta2-adrenergic agonist therapy ameliorate experimental autoimmune myocarditis in a rat model?
Beta2-adrenergic receptor stimulation suppresses the development of experimental autoimmune myocarditis in rats, suggesting potential as a novel immunomodulatory therapy.
BACKGROUND: The therapeutic potential of beta2-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 beta2-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 beta1-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 beta2-selective AR agonists inhibited the activation of cardiac myosin fragment-specific myocarditogenic T lymphocytes, and this effect was reversed by ICI118,551, a beta2-selective AR antagonist. Furthermore, treatment with 2 different beta2-selective AR agonists starting on day 14 also ameliorated EAM on day 21. CONCLUSIONS: beta2-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. beta2-AR-stimulating agents may represent important immunomodulators of the cardiac myosin-induced autoimmune process and have potential as a new therapy for myocarditis.
Nishii et al. (Tue,) conducted a other in Experimental autoimmune myocarditis. beta2-selective AR agonists (formoterol or salbutamol) vs. Propranolol, metoprolol, or control was evaluated on Amelioration of experimental autoimmune myocarditis on day 21. Beta2-selective AR agonists (formoterol or salbutamol) ameliorated experimental autoimmune myocarditis in rats on day 21 and increased myocardial IL-10/IFN-gamma mRNA levels.