title: Role of interferon in the protective effect of an immunomodulator derived from the Su strain of Streptococcus pyogenes A3 against viral myocarditis in mice.
abstract: OK432 (preparation derived from the Su strain of Streptococcus pyogenes A3; Picibanil, CAS 39325-01-4) is an immunomodulator. The treatment of mice with OK432 enhances their resistance to encephalomyocarditis virus (EMCV) along with a concomitant increase of interferon (IFN) titer and natural killer (NK) cell activity. To ascertain whether IFN or NK cell activity may play a crucial role in the mechanism of resistance, we compared these strains: EMCV resistant C57BL mice, C3H mice with myocarditis and DBA/2 mice with both myocarditis and diabetes mellitus. Although IFN production in all three kinds of mice was significantly increased on day 3 after inoculation, NK cell activity in EMCV resistant C57BL mice was significantly lower than that in C3H and DBA/2 mice. The lower antiviral resistance of mice treated with both OK432 and anti-interferon antibody (aIFN) was accompanied by a reduction of serum IFN titer, irrespective of the reduction in NK cell activity. Decreased activation of NK cells by anti-asialo GM1 monoclonal antibody (aNK) of OK432-treated mice also resulted in higher viral titers. However, these titers of both OK432 and aNK-treated mice were significantly lower than those of both OK432 and aIFN-treated mice. The degree of elevation of viral titer showed the following trend: OK432 and a IFN-treated mice > OK432 and aNK-treated mice >> OK432-treated mice. Moreover, histological changes of the heart in OK432 and aIFN-treated mice were significantly (p < 0.05) more severe than that in OK432 and aNK-treated and that in OK432-treated infected mice 7 days after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Gunma University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kanda
authors.forename: T
authors.initials: T
authors.lastname: Yokoyama
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Murata
mesh_terms: D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000627:therapeutic use*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D004686:Encephalomyocarditis virus; D004769:Enterovirus Infections / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D007372:Interferons / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009205:Myocarditis / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D010844:Picibanil / Q000627:therapeutic use*; D013297:Streptococcus pyogenes / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D010844:Picibanil; D007372:Interferons