Sunlight, immunosuppression and skin cancer: Role of histamine and mast cells

1. The development into tumours of skin cells transformed by ultraviolet (U V) B radiation of wavelengths 290-320 nm is enhanced by the ability of UVB to suppress an immune response that mould otherwise destroy them, Ultraviol et B-induced immunomodulation may be by multiple mechanisms, but generally manifests in an antigen-presenting cell defect and an altered cytokine envi ronment in the draining lymph nodes. 2. Immune responses to microbial or self-antigens may be dysfunctional by s imilar mechanisms following UVB exposure. 3. Earliest-acting intermediates in the initiation of UVB-induced immunosup pression are the UVB absorbers (photoreceptors) of the skin, notably DNA re sulting in immunoregulatory cytokine production, and trans-urocanic acid (U CA), which, upon isomerization to its cis isomer, signals downstream immuno suppressive events. 4. In mice, dermal mast cells are critical to UVB-induced systemic immunomo dulation, In mice, there is a functional link as well as a linear relations hip between the prevalence of histamine-staining dermal mast cells and the log of the dose of UVB required for 50% immunosuppression, Studies with his tamine receptor antagonists support histamine as the main product of mast c ells involved. Histamine acts in targe part via a prostanoid dependent path way. 5. Approximately 50% of humans and greater than 90% of patients with non-me lanoma skin cancer are UVB susceptible for suppression of a contact hyperse nsitivity response. Neither cytokine polymorphisms nor UVB-induced levels o f cis-UCA in irradiated skin have been linked to UVB susceptibility. Patien ts with basal cell carcinomas (BCC) have an increased dermal mast cell prev alence in non-sun-exposed buttock skin. We propose that mast cells function in humans, as in mice, by initiating immunosuppression and, thereby, allow ing a permissive environment for BCC development.