STIMULATION OF HAIR-GROWTH BY TOPICAL APPLICATION OF FK506, A POTENT IMMUNOSUPPRESSIVE AGENT

FK506, a macrolide antibiotic produced by Streptomyces tsukubaensis, is known as a potent T cell - specific immunosuppressant, and is effective against graft rejection after organ transplantation. Topical application of FK506 (0.03-1 mu mol) to dorsal skin of CD-1 mice stimulated hair growth in a dose-dependent manner. Unlike topical application, oral administration of 30 mg/kg of FK506, a dose that induces marked immunosuppression, did not stimulate significant hair growth. Topical application of FK506 also stimulated hair growth of rats and Syrian golden hamsters. FK506 stimulated hair growth even in SCID mice that lack both B- and T-cell immunity. Therefore,, it is unlikely that the hair growth - stimulatory effect of FK506 results from its immunosuppressive effect. FK506 (0.01-1 mu M) stimulated both [H-3]thymidine and [H-3]glycine uptakes to cultured mouse vibrissae follicles in a concentration-dependent manner. Moreover, when the follicles were treated with FK506 (1 mu M) for 16 d, the size of the follicles (length of hair plus follicle) increased slightly but significantly. On the other hand, the size of the non-treated follicles did not increase significantly. These results indicate that FK506 directly stimulates hair follicles. Long-term treatment of mice with FK506, i.e., topical application of 1 mu mol FK506 twice a week for 6 months, did not affect body weight gain of mice, and the FK506-treated mice looked healthy. FK506 may be useful as a stimulant of hair growth.