Sunlight, Immunosuppression And Skin Cancer: Role Of Histamine And Mast Cells

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Abstract
SUMMARY: 1. The development into tumours of skin cells transformed by ultraviolet (UV) B radiation of wavelengths 290–320 nm is enhanced by the ability of UVB to suppress an immune response that would otherwise destroy them. Ultraviolet B‐induced immunomodulation may be by multiple mechanisms, but generally manifests in an antigen‐presenting cell defect and an altered cytokine environment in the draining lymph nodes.2. Immune responses to microbial or self‐antigens may be dysfunctional by similar mechanisms following UVB exposure.3. Earliest‐acting intermediates in the initiation of UVB‐induced immunosuppression are the UVB absorbers (photoreceptors) of the skin, notably DNA resulting in immunoregulatory cytokine production, and trans‐urocanic acid (UCA), which, upon isomerization to its cis isomer, signals downstream immunosuppressive events.4. In mice, dermal mast cells are critical to UVB‐induced systemic immunomodulation. In mice, there is a functional link as well as a linear relationship between the prevalence of histamine‐staining dermal mast cells and the log of the dose of UVB required for 50% immunosuppression. Studies with histamine receptor antagonists support histamine as the main product of mast cells involved. Histamine acts in large part via a prostanoid‐dependent pathway.5. Approximately 50% of humans and greater than 90% of patients with non‐melanoma skin cancer are UVB susceptible for suppression of a contact hypersensitivity response. Neither cytokine polymorphisms nor UVB‐induced levels of cis‐UCA in irradiated skin have been linked to UVB susceptibility. Patients with basal cell carcinomas (BCC) have an increased dermal mast cell prevalence in non‐sun‐exposed buttock skin. We propose that mast cells function in humans, as in mice, by initiating immunosuppression and, thereby, allowing a permissive environment for BCC development.

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