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Effect of immunostimulant therapy on acute viral myocarditis in an animal model
1Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
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)-alan ine), 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 less than 0.05; 3.55 +/- 0.23, control: 5.64 +/- 0.09, p less than 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 less than 0.025) and increased survival (70% and 60%, respectively, control: 20%, p less than 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 less than 0.05) and myocardial necrosis (1.2 +/- 0.42, control: 2.0 +/- 1.00, p less than 0.025). The present study suggests that immunostimulant therapy improves the course of viral myocarditis during the virus-mediated phase.(ABSTRACT TRUNCATED AT 250 WORDS)
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)-alan ine), 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 less than 0.05; 3.55 +/- 0.23, control: 5.64 +/- 0.09, p less than 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 less than 0.025) and increased survival (70% and 60%, respectively, control: 20%, p less than 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 less than 0.05) and myocardial necrosis (1.2 +/- 0.42, control: 2.0 +/- 1.00, p less than 0.025). The present study suggests that immunostimulant therapy improves the course of viral myocarditis during the virus-mediated phase.(ABSTRACT TRUNCATED AT 250 WORDS)