Inhibition of Skin Allograft Rejection and Acute Graft-Versus-Host Disease by Cis-Urocanic Acid

Ultraviolet B radiation initiates a suppression of the delayed-type hypersensitivity response accompanied by a generation of antigen-specific suppressor cells and an alteration of antigen-presenting function. In previous studies we and other investigators could achieve a prolongation of graft survival by a treatment of the recipient with UVB light or 8-methoxypsoralen plus UVA light (PUVA). One of the mediators of the systemic immunomodulatory effects of ultraviolet light or PUVA may be urocanic acid, which is isomerized in the skin by ultraviolet light from its cis- to the trans-isomer. In this work we present evidence that cis-urocanic acid, generated in vitro by a treatment with UVB light or PUVA, is able to prolong the survival of allogeneic MHC disparate skin grafts in mice. In contrast, the rejection of second set grafts was not suppressed. Unirradiated (trans-urocanic acid) had no effect on allograft rejection. In a murine model cis-, but not trans-urocanic acid, prevented or delayed an acute lethal graft-versus-host disease. These experiments demonstrate the potent systemic immunomodulatory effects of cis-urocanic acid in vivo