Preventive effects of OK432 on murine acute myocarditis due to encephalomyocarditis virus

Abstract

OK432, one of the immunomodulators used for cancer treatment in Japan was examined for its effects on murine myocarditis due to encephalomyocarditis (EMC) virus. The survival rate of mice administered with 1 KE of OK432 intraperitoneally every other day starting 2 days before viral inoculation was significantly higher than that of the control mice administered virus alone on days 10-21 (16/20 vs. 4/20, p less than 0.001), and the viral titer in the heart, the heart weight/body weight ratio, and the scores for myocardial inflammation and necrosis were significantly lower. The natural killer (NK) cell activity and interferon (IFN) titer on day 1 after infection were increased in comparison with the control group (NK cell activity: 51.1 vs. 37.9%, p less than 0.05. IFN: 1205 vs 512 U/ml), and the cytotoxicity of peritoneal macrophages was increased (50.6 vs. 29.1%). Thus, OK432 given before viral inoculation significantly improved survival and reduced both the viral titer in the heart and myocardial damage in this experimental model of acute EMC viral myocarditis. Accordingly, the stimulation of the host immunologic response by OK432 may be important for elimination of virus of the heart.