EFFECT OF IMMUNOSTIMULANT THERAPY ON ACUTE VIRAL MYOCARDITIS IN AN ANIMAL-MODEL

The effect of immunostimulant therapy on acute viral myocarditis, which was induced with encephalomyocarditis virus, was investigated in 4-week-old male BALB/c mice. In vitro, peritoneal exudate cells and spleen cells from mice that were pretreated with a synthetic immunoactivating peptide, FK565 (heptanoyl-gamma-D-glutamyl-(L)-meso-diaminopimelyl-(D)-alanine), significantly inhibited the multiplication of encephalomyocarditis virus in BALB/c 3T3 cells compared with peritoneal exudate cells and spleen cells from untreated mice (6.14 +/- 0.21 log10 plaque-forming units (pfu) per milliliter, control: 6.59 +/- 0.03, p < 0.05; 3.55 +/- 0.23, control: 5.64 +/- 0.09, p < 0.01, respectively), although FK565 did not inhibit viral replication directly. The mice were inoculated intraperitoneally with 100 pfu of encephalomyocarditis virus. FK565 (1 mg/kg/day), which was administered 1 day before or simultaneously with virus inoculation, effectively inhibited myocardial viral replication (2.77 +/- 0.17 log10 pfu/mg, 2.46 +/- 0.35, log10 pfu/mg, respectively, control: 3.33 +/- 0.26, p < 0.025) and increased survival (70% and 60%, respectively, control: 20%, p < 0.01). Histopathologic findings were scored on a scale of 0 to 4. Treatment with 1 mg/kg/day of FK565 that was started 1 day before virus inoculation was most effective in reducing the inflammatory response (1.2 +/- 0.63, control: 2.0 +/- 0.81, p < 0.05) and myocardial necrosis (1.2 +/- 0.42, control: 2.0 +/- 1.00, p < 0.025). The present study suggests that immunostimulant therapy improves the course of viral myocarditis during the virus-mediated phase. The inhibitory activity of FK565 seems to be due to the activation of host defense mechanisms such as macrophages or lymphocytes.