To test the therapeutic efficacy of immunosuppression with cyclophosphamide (CYP) on coxsackievirus B3 (CB3) myocarditis, 2-week-old DBA/2 mice were inoculated 3 x 102 plaque-forming units of CB3 virus. CYP (100 mg/kg/day s.c.) was administered daily on days 0-8 (experiment 1; group 2), days 8-21 (experiment 2; group 4), and days 21-34 (experiment 3; group 6). Group 1, 3, and 5 were infected control groups for each experiment. Spleen, thymus, and body weights were measured. In experiment 1, survival rate in group 2 on day 8 was low compared with group 1 (nine of 51 versus eight of 28; p = NS), and myocardial virus titers in group 2 on day 8 were higher (p < 0.05) compared with group 1; however, cellular infiltration and myocardial necrosis in group 2 were less severe (p < 0.05), and serum neutralizing antibody titers were decreased (p < 0.01). In experiment 2, survival rate in group 4 on day 21 was significantly lower (six of 24 versus 12 of 16; P < 0.01), but cellular infiltration, myocardial necrosis, and calcification in group 4 were significantly less severe, and serum neutralizing antibody titers were decreased (p < 0.01). In experiment 3, survival rate, cardiac histopathology, and serum neutralizing antibody titers did not differ between groups 5 and 6. In experiments 1, 2, and 3, the treated groups were characterized by lower spleen-to-body-weight and thymus-to-body-weight ratios and by marked cellular depletion in spleen and thymus. A similar reduction of cardiac histopathology, associated with lymphoid organ atrophy in the treated group, was demonstrated in the early study (day 4) in experiment 1. Thus, the administration of CYP (100 mg/kg/day) induced immunosuppression in CB3 myocarditis in mice. Notwithstanding an associated higher mortality rate, the severity of cardiac pathology was reduced in the acute stage. However, no beneficial effects were seen in the later stage. It is concluded that immune mechanisms play a role in the early stage of development of CB3 myocarditis.
