Therapeutic effects of streptococcal preparation OK-432 on atopic dermatitis-like lesions in NC/Nga mice: possible shift from a Th2- to Th1-predominance.

Background: The inducement of Th1 cell-mediated immune response, possibly brought about through bacterial stimulation, may serve to control atopic disorders such as atopic dermatitis (AD). The streptococcal preparation, OK-432, has been shown a potent Th1 inducer through the action of IL-12. NC/Nga mice under ordinary conditions have been found to contract dermatitis similar to human AD.

Objective: Examination was made of the therapeutic effects of OK-432 local intra- and/or subcutaneous injections on AD-like lesions in NC/Nga mice.

Methods: Immunohistochemical staining with IL-4/IL-12p40 and CD80/86 and phosphorylated STAT4/p-STAT6 and RT-PCR for IL-4/IL-12p40 and STAT6/STAT4 mRNA was conducted for the evaluation of OK-432 treatment of spontaneous AD-like lesions in NC/Nga mice.

Results: At 5 weeks following injection of OK-432, for treating head and back lesions in NC/Nga mice, 10 of 12 OK-432 treated NC mice were found to have clinically improved quite considerably. On the head and back skin of OK-432-treated mice, IL-12p40/CD80 positive cellular infiltration was conspicuous, in contrast to non-treated mice. IL-4/CD86 positive cellular infiltrates in OK-432-treated mice had decreased significantly more than in non-treated mice and IL-4 mRNA expression was virtually absent in OK-432-treated mice. P-STAT4 positive cells could be seen abundantly present in OK-432-treated mice, and p-STAT6 positive cells were much fewer than in non-treated mice.

Conclusions: OK-432-treatment appears to induce Th1 cellular response and to down-regulate that of the Th2 pathway in AD-like lesions of NC/Nga mice. The present results demonstrate bacterial components from such Streptococcus to likely constitute an effective new therapeutic approach in the treatment of AD.