Cyclosporin A (CsA), a cyclic endecapeptide, is a T cell-specific
immunosuppressant and is successfully used in the field of
organ transplantation. Another T cell-specific
immunosuppressant,
FK506, a more recently discovered
macrolide antibiotic, is effective against graft rejection at much lower doses than CsA. Although totally different in structure, both compounds inhibit T cell activation by interfering with the production of
interleukin-2 (IL-2) by inhibiting
IL-2 gene expression, probably through the inhibition of
calcineurin, a Ca2+/
calmodulin-dependent
phosphatase. Clinical studies have revealed that
FK506 induces a variety of side effects in common with CsA. One of the most common side effects of CsA is
hypertrichosis. The hair growth stimulating effect of CsA is observed not only in normal but also in pathological conditions of hair growth, i.e. in patients with
alopecia areata and also in some patients with
male-pattern alopecia. Although
hypertrichosis is induced by both topical and
oral administration of CsA, there has been no report showing that
FK506 induces
hypertrichosis. Recently we have found that topical application of
FK506 to skins of mice, rats and hamsters markedly stimulates hair growth. This hair growth stimulating effect of
FK506 is observed when applied topically but not by
oral administration, even with a dose which causes marked immunosuppression. The hair growth stimulating effect of
FK506 in normal animals may apparently be unrelated to its immunosuppressive effect. In vitro studies revealed that
FK506 directly stimulates hair follicles. Mechanisms of hair growth stimulating effects of
FK506 and CsA remain to be elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)