Hair growth modulation by topical immunophilin ligands: induction of anagen, inhibition of massive catagen development, and relative protection from chemotherapy-induced alopecia.
Selected immunophilin ligands (IPLs) are not only potent immunosuppressants but also modulate hair growth. Their considerable side effects, however, justify at best topical applications of these drugs for the management of clinical hair growth disorders. Therefore, we have explored hair growth manipulation by topical cyclosporin A (CsA) and FK 506 in previously established murine models that mimic premature hair follicle regression (catagen) or chemotherapy-induced alopecia, two major pathomechanisms underlying human hair loss. We confirm that topical CsA and FK 506 induce active hair growth (anagen) in the back skin of C57BL/6 mice with all follicles in the resting stage (telogen) and show that both IPLs also inhibit massive, dexamethasone-induced, premature catagen development in these mice. Furthermore, we demonstrate that CsA and FK 506 provide relative protection from alopecia and follicle dystrophy induced by cyclophosphamide, possibly by favoring the dystrophic anagen pathway of follicle response to chemical damage. Although it remains to be established whether these IPLs exert the same effects on human hair follicles, our study provides proof of the principle that topical IPLs can act as potent manipulators of clinically relevant hair-cycling pathomechanisms. This strongly encourages one to explore the use of topical IPLs in the management of human hair growth disorders.
Maurer
M
M
Department of Dermatology, Charité Hospital, Humboldt-Universität zu Berlin, Germany.
Handjiski
B
B
Paus
R
R
D000287:Administration, Topical; D000505:Alopecia / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D003520:Cyclophosphamide / Q000633:toxicity; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003907:Dexamethasone / Q000031:analogs & derivatives / Q000633:toxicity; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D018859:Hair Follicle / Q000187:drug effects* / Q000254:growth & development*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D008024:Ligands; D003907:Dexamethasone; D016572:Cyclosporine; D003520:Cyclophosphamide; C018038:dexamethasone acetate; D016559:Tacrolimus