Prolongation of Murine Skin Allograft Survival by the Systemic Effects of 8-Methoxypsoralen and Long-wave Ultraviolet Radiation (PUVA)

Abstract

Systemic administration of the photoactive drug 8-methoxypsoralen to a group of mice bearing cutaneous allografts, followed by exposure to long-wave ultraviolet radiation (UVA, 320-400 nm) (PUVA) daily for 14 days at a site distant from the allograft, significantly increased the survival time of the allografts. This effect was seen both in donor-recipient combinations that differ at the major histocompatibility complex and in those differing only at minor histocompatibility loci. Treatment with 8-methoxypsoralen or long-wave UV radiation alone was ineffective in prolonging allograft survival, as were doses of mid-wave UV radiation (UVB, 280-320 nm) that produced greater inflammation than the PUVA protocol. Allografted, PUVA-treated animals also demonstrated decreased alloantigen reactivity against donor-strain spleen cells during the period of treatment by cytotoxicity assays. Allografts of skin in the murine system are highly immunogenic and are generally rejected faster than organ allografts; thus PUVA treatment appears to exert a potent effect on prolonging allograft survival. The systemic nature of the effect and the fact that adverse side effects from PUVA are largely limited to the skin suggest that PUVA might have a role in clinical organ transplantation management.