Treatment of coxsackievirus B3 myocarditis by immunoactive peptide in an animal model.

The effect of immunostimulant therapy on acute viral myocarditis, induced with coxsackievirus B3 (CB3), was investigated in C3H/He mice. Peritoneal exudate cells (PEC) or spleen cells (SC) from mice pretreated with a synthetic immunoactivating peptide FK565 significantly inhibited the multiplication of CB3 in C3H/He mouse embryo fibroblast cells compared with PEC or SC from nontreated mice in vitro (6.45 +/- 0.20 log10 PFU/ml; control: 6.85 +/- 0.05, P < 0.05; 6.40 +/- 0.07, control: 6.78 +/- 0.07, P < 0.05, respectively), although FK565 did not inhibit viral replication directly. Mice were inoculated intraperitoneally with 3 x 10(5) plaque-forming units of CB3. FK565, 1 or 10 micrograms/kg, given intraperitoneally daily started on the same day of viral inoculation. To determine CB3 virus titer, mice were killed on Day 3. To study survival and myocardial histopathology, mice were killed on Day 20. Histopathological findings were scored on a scale of 0 to 4. FK565, 10 micrograms/kg/day, effectively inhibited myocardial viral replication (3.23 +/- 0.42 log10 PFU/mg, control: 3.71 +/- 0.40, P < 0.05), reduced the cellular infiltration (1.3 +/- 0.7, control: 2.5 +/- 0.5, P < 0.05), myocardial necrosis (1.4 +/- 0.9, control: 3.0 +/- 0.6, P < 0.01), and calcification of the heart (1.0 +/- 0.6, control: 2.5 +/- 0.5, P < 0.01) and increased survival (60%, control: 30%, P < 0.05). The present study suggests that immunostimulant therapy improves the course of viral myocarditis during the viral-mediated phase. The inhibitory activity of FK565 seems to be due to the activation of host defense mechanisms.