Combination therapy of OK432 and recombinant human interferon alpha A/D on viral myocarditis in mice starting after infection.
We investigated the effects of OK432, recombinant human interferon alpha A/D (rIFN alpha A/D) and a combination of these drugs on murine acute myocarditis due to encephalomyocarditis virus. Mice were administered 1 KE of OK432 and 10(4)U/g of rIFN alpha A/D starting 24 hr after viral inoculation for 14 days. The survival rate of mice having the combination therapy was significantly higher than that of untreated mice on day 21 (15 of 20 vs. 6 of 20, P less than .001), whereas the viral titer in the heart, the heart weight/body weight ratio and the scores for myocardial inflammation and necrosis were significantly lower. On the other hand, therapy with OK432 or rIFN alpha A/D individually improved neither the survival rate nor the extent of myocardial damage. The natural killer cell activity in the combination therapy mice on day 3 after infection was significantly increased in comparison with untreated mice (46.2 +/- 5.5 vs. 37.7 +/- 2.8%, P less than .01), and the cytotoxicity of peritoneal macrophages was increased (45.0 vs. 26.7%). Thus, the combination therapy of OK432 and rIFN alpha A/D was more effective than the therapy with OK432 alone or rIFN alpha A/D alone against acute viral myocarditis when the treatment was started early after infection, and the stimulation of host immunologic response by OK432 may be important for this combination therapy.
Yokoyama
T
T
Second Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Kanda
T
T
Suzuki
T
T
Murata
K
K
D000818:Animals; D001835:Body Weight / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004359:Drug Therapy, Combination; D004686:Encephalomyocarditis virus; D005260:Female; D006321:Heart / Q000033:anatomy & histology; D007370:Interferon Type I / Q000097:blood / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000188:drug therapy* / Q000382:microbiology; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D010844:Picibanil / Q000627:therapeutic use*; D011994:Recombinant Proteins
D007370:Interferon Type I; D011994:Recombinant Proteins; D010844:Picibanil