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.
Horiuchi
Yasuhiro
Y
Department of Dermatology, Nagaski University School of Medicine, 1-7-1 Sakamoto, Nagasaki, Japan. nu-yhori@jcom.home.ne.jp
Bae
SangJae
S
Katayama
Ichiro
I
Nishioka
Kiyoshi
K
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D010844:Picibanil / Q000494:pharmacology*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; D012867:Skin / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D000970:Antineoplastic Agents; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C499538:Ccl17 protein, mouse; C497965:Cd86 protein, mouse; D054414:Chemokine CCL17; D019742:Chemokines, CC; D004268:DNA-Binding Proteins; D053762:Interleukin-12 Subunit p40; D008562:Membrane Glycoproteins; D021122:Protein Subunits; D012333:RNA, Messenger; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; C494091:Stat4 protein, mouse; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12; D015847:Interleukin-4; D010844:Picibanil