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)-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)
Sato
Y
Y
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Maruyama
S
S
Kawai
C
C
Matsumori
A
A
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D004686:Encephalomyocarditis virus / Q000502:physiology; D004769:Enterovirus Infections / Q000276:immunology / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology / Q000382:microbiology* / Q000628:therapy; D009842:Oligopeptides / Q000627:therapeutic use*; D014779:Virus Replication / Q000187:drug effects
D000276:Adjuvants, Immunologic; D009842:Oligopeptides; C039537:heptanoyl-gamma-D-glutamyl-L-meso-diaminopimelyl-D-alanine