Effects of FK506 (tacrolimus hydrate) on chronic oxazolone-induced dermatitis in rats.
Chronic allergic contact dermatitis was induced in rat ear by repeated application of oxazolone. This dermatitis was accompanied by sustained ear swelling and marked epidermal hyperplasia. In the induced ear, there was marked inflammatory cell infiltration into the dermis site and the interferon-gamma amount increased in both protein and mRNA, while the interleukin-4 amount changed minimally. Topical administration of FK506 (tacrolimus hydrate) dramatically suppressed ear swelling and epidermal hyperplasia as well as the increase in interferon-gamma expression. Betamethasone valerate also showed suppressive effects, but 1,25-dihydroxyvitamin D(3) (calcitriol) had no effect. These results suggest that interferon-gamma plays an important role in dermatitis and this model could be a useful pharmacological model for chronic dermatitis featuring epidermal hyperplasia in which interferon-gamma plays a crucial role, such as psoriasis. FK506 demonstrating suppressive effects as potent as those of betamethasone valerate shows potential as a topically usable drug for such skin disorders.
Fujii
Yasutomo
Y
Department of Immunology and Inflammation, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan. yasutomo_fujii@po.fujisawa.co.jp
Takeuchi
Hiroko
H
Tanaka
Keiko
K
Sakuma
Shozo
S
Ohkubo
Yoshitaka
Y
Mutoh
Seitaro
S
D000818:Animals; D001623:Betamethasone / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D017449:Dermatitis, Allergic Contact / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D004423:Ear / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005938:Glucocorticoids / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D010081:Oxazolone / Q000008:administration & dosage; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016559:Tacrolimus / Q000494:pharmacology*
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D010081:Oxazolone; D015847:Interleukin-4; D007371:Interferon-gamma; D001623:Betamethasone; D002117:Calcitriol; D016559:Tacrolimus