The effects of FK-506, a novel and potent immunosuppressant, upon murine Coxsackievirus B3 myocarditis.
To test the therapeutic efficacy of immunosuppression with FK-506 upon coxsackievirus B3 myocarditis, C3H/He mice were inoculated with coxsackievirus B3, and the effects of FK-506 were compared to those of cyclosporine. FK-506 (2.5 mg/kg/day) or cyclosporine (25 mg/kg/day) was administered s.c. daily on days 0 to 14 (experiment I) and on days 14 to 28 (experiment II). In experiment I, the survival rate of the FK-506 or cyclosporine-treated group was significantly lower compared with that of the untreated, control group. However, the score of myocardial cellular infiltration in both treated groups was lower compared to the control. On day 14, myocardial virus was not detected in the control group, but was present in both treated groups. Serum neutralizing antibody titers on day 14 in FK-506 group were lower than in the control group. In experiment II, survival rate did not differ significantly among the three groups. Serum-neutralizing antibody titers on day 21 in FK-506 group were lower than in the control. Histologically, marked cellular depletion in the thymus and spleen was evident in FK-506 groups; in cyclosporine groups, it was only evident in the thymus. Thus, FK-506 induced immunosuppression in coxsackievirus B3 myocarditis, associated with a high mortality, notwithstanding the reduction of myocardial cellular infiltration in the acute stage when immune mechanisms play a role in the pathogenesis of the disease. With respect to the dosage, the immunosuppressive action of FK-506 in vivo is at least 10-fold stronger compared to that of cyclosporine.
Hiraoka
Y
Y
Second Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Kishimoto
C
C
Kurokawa
M
M
Ochiai
H
H
Sasayama
S
S
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D029822:Enterovirus B, Human / Q000187:drug effects* / Q000276:immunology / Q000302:isolation & purification; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use*
D000914:Antibodies, Viral; D016559:Tacrolimus