picibanil and Enterovirus-Infections

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)

Topics: Adjuvants, Immunologic; Animals; Antibodies; Diabetes Mellitus, Experimental; Encephalomyocarditis virus; Enterovirus Infections; Interferons; Killer Cells, Natural; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred DBA; Myocarditis; Myocardium; Picibanil; Streptococcus pyogenes

Immune modulators injected 24 h before encephalomyocarditis virus significantly increase antiviral resistance in mice when interferon is administered 1 h after the virus. These immune modulators can be crude bacterial extracts or synthetic drugs. In some cases, the responses are additive; in others, they are clearly cooperative. To protect the mice against the development of 180 TG Crocker sarcomas, the association of bacterial extracts and interferon is highly effective under the condition that the drug concentrations and chronological order and number of injections are well defined. In contrast, the conjunction of interferon and synthetic immune modulators, in particular cimetidine, result in delayed tumor development with no significant change in the final survival rate in the experimental model described here.

Topics: Adjuvants, Immunologic; Animals; Carcinoma, Ehrlich Tumor; Cimetidine; Ditiocarb; Encephalomyocarditis virus; Enterovirus Infections; Interferon Type I; Mice; Peptides, Cyclic; Picibanil; Sarcoma 180