Immunosuppressive macrolides of the type FK 506: a novel class of topical agents for treatment of skin diseases?
The immunosuppressive macrolide antibiotics FK 506 and rapamycin were tested for topical activity in experimental allergic contact dermatitis of farm pigs. This species was used because pig skin, in comparison to rodent skin, resembles human skin more closely. For comparison, cyclosporine A (CyA), which is orally but not topically active in patients with skin disease, dexamethasone, and clobetasol propionate were used. Treatment was performed twice, 30 min and 6 h after elicitation of challenge reaction. Topical application of 0.4 to 0.04% FK 506 caused a pronounced inhibition of inflammatory skin reactions of hypersensitivity to dinitrofluorobenzene. The treatment response was similar to the activity of 0.13% clobetasole. Dexamethasone (1.2%) was less active than clobetasol. In contrast, rapamycin and CyA were inactive at concentrations of 1.2 and 10%, respectively. Because the pig data on corticosteroids and cyclosporine A are in agreement with clinical findings, these studies indicate that immunosuppressive macrolides of the type FK 506 may be useful drugs for the topical treatment of human skin diseases that respond to local corticosteroids and oral treatment with cyclosporine A.
Meingassner
J G
JG
Department of Dermatology, Sandoz Forschungsinstitut, Vienna, Austria.
Stütz
A
A
D000818:Animals; D002990:Clobetasol / Q000627:therapeutic use; D016572:Cyclosporine / Q000737:chemistry / Q000627:therapeutic use; D003877:Dermatitis, Contact / Q000188:drug therapy*; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D015394:Molecular Structure; D011090:Polyenes / Q000737:chemistry / Q000627:therapeutic use; D020123:Sirolimus; D013552:Swine; D016559:Tacrolimus / Q000737:chemistry / Q000627:therapeutic use*
D011090:Polyenes; D003907:Dexamethasone; D016572:Cyclosporine; D002990:Clobetasol; D020123:Sirolimus; D016559:Tacrolimus