RELATIONSHIP BETWEEN ULTRAVIOLET-RADIATION - INDUCED IMMUNOSUPPRESSION AND CARCINOGENESIS

The capacity of ultraviolet B (UVB) radiation to damage the cutaneous immune system has been extensively documented and there is good reason to believe that UVB-induced damage is a critical, albeit permissive, factor in the development of sunlight-induced skin cancers. A summary of the evidence shows that acute, low-dose UVB protocols, which resemb le quantitatively and qualitatively the manner in which human beings t ypically experience sun exposure, alter the cutaneous immune system in at least two important ways: they impair the induction of contact hyp ersensitivity to cutaneous antigens, and induce antigen-specific toler ance. In mice there is compelling evidence that immunogenetic factors dictate whether UVB radiation will impair contact hypersensitivity ind uction or not. The genetic loci that contain the relevant polymorphic alleles include tumor necrosis factor-alpha and lipopolysaccharide. Be cause the effects of UVB radiation on contact hypersensitivity inducti on are mimicked by intracutaneous injections of subinflammatory doses of tumor necrosis factor-alpha or cis-urocanic acid, the favored hypot hesis to explain the mechanism of action of UVB radiation in UVB-susce ptible individuals is that UVB-dependent transformation of trans- to c is-urocanic acid in the epidermis triggers the intracutaneous release of excess amounts of tumor necrosis factor-alpha. By transiently immob ilizing Langerhans cells and other local antigen-presenting cells with in the skin, the requirement that hapten be brought to the draining ly mph node to sensitive naive hapten-specific T cells is not met, and co ntact hypersensitivity fails to develop. Because the UVB-susceptibilit y and UVB-resistance traits have also been demonstrated in human being s, the hypothesis is advanced that these traits are similarly under co ntrol of immunogenetic factors, and that a constellation of immune sus ceptibility genes contributes to the risk of developing sunlight-induc ed skin cancer. The cellular and molecular basis of UVB-induced tolera nce is not as well described, but current evidence suggests that diffe rent mechanisms, and presumably different polymorphic genes, dictate w hether tolerance will emerge after UVB exposure in mice. Because acute , low-dose UVB also induces tolerance in human beings, the immunogenet ic factors that dictate tolerance of this type may also contribute to the risk of developing sunlight-induced skin cancer.