Junichi Nakahata

β2-Adrenergic Agonists Suppress Rat Autoimmune Myocarditis Potential Role of β2-Adrenergic Stimulants as New Therapeutic Agents for Myocarditis

Background— The therapeutic potential of β2-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 β2-selective AR agonists formoterol or salbutamol ameliorated EAM on day 21 and increased myocardial interleukin-10/interferon-γ mRNA levels. Propranolol, a nonselective β-AR antagonist, aggravated EAM on day 21 and decreased mRNA levels, whereas metoprolol, a β1-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 β2-selective AR agonists inhibited the activation of cardiac myosin fragment–specific myocarditogenic T lymphocytes, and this effect was reversed by ICI118,551, a β2-selective AR antagonist. Furthermore, treatment with 2 different β2-selective AR agonists starting on day 14 also ameliorated EAM on day 21. Conclusions— β2-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. β2-AR–stimulating agents may represent important immunomodulators of the cardiac myosin–induced autoimmune process and have potential as a new therapy for myocarditis.

Fulminant Myocarditis—From Lethal Disease to Survival

Fulminant myocarditis is a representative lethal heart disease, in which patients have only been urgently rescued with the help of mechanical cardiopulmonary supports. Nevertheless, the therapeutic outcomes of fulminant myocarditis treated with PCPS has not been elucidated. Recently, a national survey was conducted to undertake these tasks by considering the current situation of patients in Japan and to propose a therapeutic guidelines for fulminant myocarditis using PCPS. Thirty (57.7%) out of 52 patients could be rescued in the survey. Important factors concerning the prognosis were the severity and improvement grade of cardiac and renal dysfunction. Based on the data, management guidelines using PCPS to improve the survival rate of fulminant myocarditis patients were published. Of the individual prognosis of patients treated with PCPS, limiting factors have not been identified even in the present survey.