picibanil and Dermatitis--Atopic

Bacterial stimulation may serve to control atopic disorders such as atopic dermatitis (AD) through inducement of Th1 cell-mediated immune response. The lipoteichoic acid (LTA)-related molecule (okLTA) from streptococcal preparation, OK-432, has been shown to be a potent Th1 inducer through the action of IL-12. Examination was made of the therapeutic effects of this okLTA injected intra- and/or subcutaneously into AD-like lesions in NC/Nga mice, particularly in the vicinity of the suppressor of cytokine signaling (SOCS) regulatory pathways. Using immunohistochemical staining with IL-4/IL-12p40 and phosphorylated STAT6/p-STAT4 and RT-PCR for IL-4/IL-12p40, STAT6/STAT4 and mRNA expression and in situ hybridization of SOCS3 and 5, evaluation was made of the immunoregulatory effects of this okLTA in the treatment of spontaneous AD-like lesions in NC/Nga mice. Following the injection of okLTA, remarkable improvement in the lesions of NC/Nga mice was noted. In okLTA-treated skin, IL-12p40/p-STAT4 positive cellular infiltration was extensive while IL-4/p-STAT6 positive cell infiltration was seen to diminish considerably, compared to untreated NC mice. SOCS3 in situ expression in okLTA-treated mice was noted to be significantly less compared to untreated NC mice, in which the expression was prominent. SOCS5 in situ expression was rather, though not significantly, strong in okLTA-treated mice. okLTA treatment is clearly shown to induce Th1 cellular response and down-regulate immune response in the Th2 pathway through SOCS3 reduction in AD-like lesions of NC/Nga mice. The present results demonstrate that bacterial wall components such as okLTA should serve as an effective new therapeutic approach for treating AD.

Topics: Animals; Anti-Inflammatory Agents; Dermatitis, Atopic; Down-Regulation; Immunohistochemistry; In Situ Hybridization; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Models, Animal; Monocytes; Picibanil; STAT6 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Teichoic Acids; Th1 Cells; Th2 Cells; Up-Regulation

Effective treatment of atopic dermatitis (AD) may in some cases prove quite difficult. OK-432, prepared from the penicillin-treated Su strain of type III Group A Streptococcus pyogenes, has been shown to be effective for treating not only cancer but verruca vulgaris as well, suggesting this agent to create the Th1 pathway through IL-12 induction. Four AD patients consented to trial use of the OK-432 ointment. OK-432 was found to bring about complete cure in the present four cases. Based on results from its use, OK-432 may be concluded to be highly effective for treating AD.

Topics: Administration, Topical; Adult; Child; Child, Preschool; Dermatitis, Atopic; Female; Humans; Male; Ointments; Picibanil

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

Topics: Animals; Antigens, CD; Antineoplastic Agents; B7-1 Antigen; B7-2 Antigen; Chemokine CCL17; Chemokines, CC; Dermatitis, Atopic; DNA-Binding Proteins; Interleukin-12; Interleukin-12 Subunit p40; Interleukin-4; Male; Membrane Glycoproteins; Mice; Mice, Inbred Strains; Picibanil; Protein Subunits; RNA, Messenger; Skin; STAT4 Transcription Factor; STAT6 Transcription Factor; Th1 Cells; Th2 Cells; Trans-Activators