Cyclosporin A-induced hair growth in mice is associated with inhibition of hair follicle regression

Background: Cyclosporin A (CsA) often causes hair growth in transplant recipients. Our objectives were to evaluate the effect of CsA on follicular hair keratinocyte growth in nude mice by assessing their proliferation in vivo, and to assess the ability of CsA to prevent follicular keratinocyte apoptosis in vivo and chemotherapy-induced keratinocyte apoptosis in vitro. Methods: Nude mice were fed various daily doses of CsA (10-100 mg/kg). Dorsal skin sections stained with hematoxylin and eosin, followed by immunostaining with 4-deoxybromouridine, were examined for determination of hair follicle number and hair follicle keratinocyte proliferation. Follicular keratinocytes were isolated and examined for apoptotic status. Apoptosis was induced in vitro in a keratinocyte cell line by 4-hydroperoxycyclophosphamide. The antiapoptotic effects of various CsA concentrations (0.1-5 μg/ml) were measured by annexin-V/propidium iodide binding. Results: CsA caused a dose-dependent increase in the number of hair follicles but had no effect on follicular keratinocyte proliferation. Treatment with CsA decreased the number of apoptotic follicular keratinocytes. In vitro, there was a dose-dependent inhibition of the extent of early and late apoptosis of treated keratinocytes. Conclusion: CsA may induce hair growth by increasing the number of hair follicles and inhibiting apoptosis of follicular keratinocytes, thereby delaying hair follicle regression.