Effect of streptococcal preparation, OK-432, on experimental infection due to Mycobacterium lepraemurium in mice of C3H/Jms strain.

Streptococcal preparation, OK-432, was examined for its therapeutic effect on experimental infection due to Mycobacterium lepraemurium (Mlm) in mice, When C3H/Jms mice (Mlm-sensitive strain) were infected with 108 Mlm to the left hind footpad, weekly injections of OK-432 via the peritoneal route (0. 1 mg dry weight per injection), it considerably enhanced elimination of organisms from the infection site during the first 6 weeks, and thereafter suppressed the growth of organisms during 6 to 23 weeks after infection. In contrast, weekly injections of OK-432 to the infection site (left hind footpad) resulted in the enhanced growth of Mlm in the infection site, indicating that multiple injections of OK-432 to the infection site might generate suppressor cells and/ or antagonizing factors against the host defense mechanisms to Mlm. We previously reported that OK-432, penicillin G-treated Streptococcus pyogenes strain Su7>, did not show any significant protective and/or therapeutic effects against infection with Mycobacterium intracellulare in mice and that multiple injections of this agent occasionally induced reduction in the host resistance to the organisms, probably due to generation of certain types of suppressor cells>. In the present study, we investigated the effects of OK-432 administration to abdominal cavity or to the infection site in mice on the host resistance to the infection due to Mycobacterium lepraemurium (Mlm), an obligate intracellular parasite. Male C3H/Jms (Mlm-sensitive) mice were infected with 108 M lepraemurium Hawaiian strain in the left hind footpad (LFP) and were given weekly doses of OK-432 (0. 03-0. 1 mg) intraperitoneally or subcutaneously to the LFP. At various intervals up to 23 weeks after infection, the mice were sacrificed and the number of Mlm in the LFP was determined according to the method of Shepard12>. Delayed type hypersensitivity (DTH) in Mlm-infected mice was tested by measuring the swelling of the right hind footpad (RFP) 24 hr after elicitation by 30 μl of Mlm-sonicate (108 bacilli equivalent). As shown in Fig. 1, the number of Mlm in the LFP of C3H/Jms mice without OK-432 treatment markedly decreased (about one log) during the first 6 weeks after infection and thereafter continuously increased over the initial inoculum until the termination of the experiment. This feature resembles that reported by Poulter and Lefford> : As they mentioned, it is felt that the elimination of Mlm from the infection site during the early phase is attributable to the expression of anti-Mlm immunity, and the subsequent continuous multiplication of Mlm is a result of generation of some immunosuppressive factors and/or suppressor cells specific to Mlm infection. In fact, antiMlm DTH response of C3H/Jms mice was considerably strong at an early phase (6 weeks) but markedly reduced at 14 weeks after infection (Table 1). Multiple intraperitoneal (ip.) injections of OK-432 induced an enhanced elimination of Mlm in the early phase, and sub*> ]\f§ ¥, 'MWi.J~§ij, ficfl!m§!i : CH3/Jms *" i/ .A vcto(rf 0 ~~!¥JM ':71 !i~~l'cto J: ~t--t1~3~fri~1fU OK-432