BACKGROUND: An increased incidence of ultraviolet-light-related skin tumours is a well-known problem in patients undergoing posttransplantation immunosuppression with systemic calcineurin inhibitors such as cyclosporine A or tacrolimus. UV-related carcinogenesis as a consequence of long-term treatment of sun-exposed sites with topical calcineurin inhibitors is therefore of theoretical concern. RESULTS: In this study, we show that tacrolimus acts as a UVB filter when incorporated into liposome membranes. In hairless mice pretreated with 1% pimecrolimus cream, 0.1% tacrolimus ointment or vehicle, the amount of epidermal thymine dimers, measured 1 h after 1 J/cm2 of UVB irradiation, was decreased by 89, 84 and 47%, respectively, as compared to untreated mice. Forty-eight hours after UVB irradiation, 97, 89 and 93% of epidermal thymine dimer levels were removed in pimecrolimus-, tacrolimus- or vehicle-treated mice, respectively. In contrast, 69% of thymine dimers, originally present in much higher amounts than in treated mice, were removed from untreated controls. UVB-induced apoptosis was less pronounced in treated mice. CONCLUSION: Taken together, these results suggest that topical calcineurin inhibitors prevent DNA photodamage due to a filter effect of both vehicle and active components, whereas they do not affect the clearance of DNA photoproducts. Copyright 2005 S. Karger AG, Basel.
BACKGROUND: An increased incidence of ultraviolet-light-related skin tumours is a well-known problem in patients undergoing posttransplantation immunosuppression with systemic calcineurin inhibitors such as cyclosporine A or tacrolimus. UV-related carcinogenesis as a consequence of long-term treatment of sun-exposed sites with topical calcineurin inhibitors is therefore of theoretical concern. RESULTS: In this study, we show that tacrolimus acts as a UVB filter when incorporated into liposome membranes. In hairless mice pretreated with 1% pimecrolimus cream, 0.1% tacrolimus ointment or vehicle, the amount of epidermal thymine dimers, measured 1 h after 1 J/cm2 of UVB irradiation, was decreased by 89, 84 and 47%, respectively, as compared to untreated mice. Forty-eight hours after UVB irradiation, 97, 89 and 93% of epidermal thymine dimer levels were removed in pimecrolimus-, tacrolimus- or vehicle-treated mice, respectively. In contrast, 69% of thymine dimers, originally present in much higher amounts than in treated mice, were removed from untreated controls. UVB-induced apoptosis was less pronounced in treated mice. CONCLUSION: Taken together, these results suggest that topical calcineurin inhibitors prevent DNA photodamage due to a filter effect of both vehicle and active components, whereas they do not affect the clearance of DNA photoproducts. Copyright 2005 S. Karger AG, Basel.