068 Cytokine Expression Modulated by Anthralin in C3H/HeJ Mice: Correlation to Efficacy on Hair Regrowth

Liping Cao, Liren Tang, John P Sundberg*, Harvey Lui, David I McLean and Jerry Shapiro; Division of Dermatology, University of British Columbia and Vancouver General Hospital, Vancouver, Canada; *The Jackson Laboratory, Bar Harbor, Maine, U.S.A.

Anthralin is one of the mostly widely using anti-psoriatic drugs and has also been suggested to have potential efficacy in alopecia areata (AA). It may have a non-specific immunomodulating effect on AA as it does in the topical treatment of psoriasis. The aim of the present study was to investigate the therapeutic effects of anthralin on AA-affected mice and the underlying mechanisms at the molecular levels. C3H/HeJ AA mice were treated daily for 12 weeks on half of the dorsal skin with 0.2 % anthralin ointment. The contra-lateral side was treated with the vehicle ointment. The percentages of surface hair coverage and hair density were graded weekly for both sides and hair growth indices were calculated using these two variables. Biopsies were taken before the treatment as baselines. At the end of the treatment, skin biopsies were collected from both treated and control sides. RNA was extracted and RNA protection assay was performed to determine the gene expression of various cytokines which might be specific for hair regrowth promotion by anthralin. Hair regrowth was observed in 9/13 (69%) mice on the treated sides. The untreated sides showed either no change or continued hair loss in all the animals. Among the cytokines tested by RPA, interfron gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) showed reduction after anthralin treatment. Interleukin 1b (IL-1b) was increased in the majority of responding mice, while decreased in 2/3 nonresponders. Similarly, IL-1 receptor antagonist (IL-1Ra) was increased in all of the responding mice by anthralin and only 1/3 of non-responders showed increased expression of IL-1Ra after treatment. We conclude that a significant number of C3H/HeJ mice with AA-like hair loss respond to topical anthralin. The molecular mechanism underlying the efficacy of anthralin on hair regrowth in this AA model might be mediated by the interplay of the cytokines produced locally in the skin.