FK506-THERAPY OF EXPERIMENTAL AUTOIMMUNE MYOCARDITIS AFTER ONSET OF THE DISEASE

Preventive effects of FK506 on autoimmune myocarditis have been demonstrated, but the therapeutic efficacy of the agent in established myocarditis yet remains to be assessed. In this study, effects of FK506 on experimental autoimmune myocarditis were investigated by the use of the agent after the onset of the disease. Lewis rats were immunized with either cardiac myosin or bovine serum albumin (BSA) in complete Freund's adjuvant. The onset of the disease was ascertained by examining randomly chosen cardiac myosin-immunized rats. Animals were divided into four groups: the BSA-immunized saline-treated group (group A, n = 6); the BSA-immunized FK506-treated group (group B, n = 6); the myosin-immunized saline-treated group (group C, n = 6); and the myosin-immunized FK506-treated group (group D, n = 11). Saline or 1.0 mg/kg/day of FK506 were intramuscularly injected from day 16 to day 27. All the rats were put to death on day 28. Rats of group C became severely ill by the third week, while in contrast, rats of group D remained active, as did rats of groups A and B. The heart weight/body weight ratio was significantly lower in group D than in group C rats. Group mean values were 3.48 +/- 0.10 gm/kg for group A, 3.48 +/- 0.16 gm/kg for group B, 4.94 +/- 0.66 gm/kg for group C, and 3.88 +/- 0.43 gm/kg for group D. Rats of group C showed severe myocarditis with mononuclear cell infiltration, myocardial necrosis, and interstitial edema. On the other hand, inflammatory cell infiltration was less prominent and fibrous tissue replaced lesions in the hearts of rats of group D. In conclusion, therapy with FK506 after the onset of the disease was shown to improve experimental autoimmune myocarditis in terms of severity and clinical course.