Prevention of viral myocarditis with recombinant human leukocyte interferon α A/D in a murine model

• Published in: Journal of the American College of Cardiology Vol. 9; no. 6; pp. 1320 - 1325
• Main Authors: Matsumori, Akira, Crumpacker, Clyde S., Abelmann, Walter H.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.1987; Elsevier Science
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Biological and medical sciences; Brain - microbiology; encephalomyocarditis virus; Encephalomyocarditis virus - isolation & purification; Enterovirus Infections - microbiology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Heart - microbiology; Humans; Immunobiology; Interferon Type I - classification; Interferon Type I - therapeutic use; Leukocytes - metabolism; Male; Mice; Mice, Inbred DBA; Miscellaneous; Myocarditis - etiology; Myocarditis - mortality; Myocarditis - pathology; Myocarditis - prevention & control; Recombinant Proteins - therapeutic use; Regulatory factors and their cellular receptors; Human; Cardiovirus; EMC virus; Picornaviridae; Alpha interferon; Rodentia; Experimental animal; Virus; Myocarditis; Prevention; Vertebrata; Mammalia; Mouse; Models
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(87)80472-2

Effects of recombinant human leukocyte interferon α A/D on experimental myocarditis due to encephalomyocarditis virus were investigated. Plaque reduction assays revealed that 50% of plaque formation in vitro in human amnion (FL) cells was inhibited by interferon α A/D (9.7 U/ml) when it was administered 24 hours before infection with the encephalomyocarditis virus. Four week old male DBA/2 mice were inoculated intraperitoneally with 10 plaque-forming units (pfu) of encephalomyocarditis virus. Interferon α A/D was administered subcutaneously (102U/g body weight per day in Group 1, 103U/g per day in Group 2 and 104U/g per day in Group 3) starting 1 day before infection. It was also administered starting the same day in Group 4 and 1 day after virus inoculation in Group 5 (104U/g per day in both groups). Control mice were injected with saline solution. Each group consisted of 10 mice; they were killed on day 4 for evaluation. Myocardial virus titers were significantly lower in Group 3 (8.2 ± 25.2 × 102pfu/mg, p < 0.05) and Group 4 (3.0 ± 5.5 × 103pfu/mg, p < 0.05) than in control mice (5.6 ± 4.1 × 104pfu/mg). Histologic examination showed extensive myocardial necrosis and cellular infiltration in all control mice, but no myocardial necrosis or cellular infiltration in Group 3 and less severe necrosis and infiltration in Group 4. There were no significant differences in myocardial virus titers or histologic changes between control mice and Group 1, 2 or 5. Thus, interferon α A/D, when administered starting before or simultaneously with virus inoculation, effectively inhibited myocardial virus replication and reduced the inflammatory response and myocardial damage in an experimental model of viral myocarditis.