GLUTATHIONE ETHYLESTER PROTECTS AGAINST LOCAL AND SYSTEMIC SUPPRESSION OF CONTACT HYPERSENSITIVITY INDUCED BY ULTRAVIOLET-B RADIATION IN MICE

Irradiation of the skin with ultraviolet B (UVB) radiation causes a lo cal and systemic suppression of T-dell-mediated immune responses. Rece ntly, N-acetylcysteine was found to protect against UVB-radiation-indu ced immunosuppression and several other types of damage induced by UV radiation. The protective effects appeared to be caused by an increase in glutathione (GSH). This increase was limited by feedback inhibitio n by GSH of its own synthesis. Better results were expected with the u se of GSH derivatives which do not require de novo synthesis, such as GSH esters. In this study, topical application of glutathione ethylest er (GSH-Et) was found to increase the epidermal GSH level in mice in a manner that was dependent on dose to 1234% of the control value at th e highest dose tested (2.0 mu mol/cm(2)). This resulted in dose-depend ent protection against UVB-radiation-induced suppression of contact hy persensitivity. The highest dose of GSM-EP tested provided 83% protect ion against local suppression and 62% protection against systemic supp ression. Immunosuppression induced by topically applied cis-urocanic a cid (cis-UCA) was prevented completely. Although an effect on the form ation of pyrimidine dimers cannot be excluded, the protective effect o f GSH-Et seems to be mediated through inhibition of the action of cis- UCA. (C) 1998 by Radiation Research Society.