Local effects of ultraviolet radiation on cutaneous immune responses

• Main Author: Duthie, Malcolm Scott
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2000
• Subjects: Cytokines; Lymphatic system; Radiation

Effects of UVR and UCA application were examined in relation to LC frequency within the epidermis. IVA1 (340-400nm) irradiation, or trans-UCA application, did not alter the LC numbers within the exposed site. UVB (280-315nm) irradiation and cis-UCA application depleted LC, and timecourses for LC depletion were established for both treatments. Injection of antibodies against either IL-1b or TNF-a before UVB irradiation or cis-UCA treatment completely abrogated their effects on LC numbers. Thus, the UVB-mediated reduction of LC is dependent on the cytokines IL-1b and TNF-a. Despite reports that UVA1 irradiation protects mice from subsequent immunosuppression by UVB exposure, UVA1 irradiation did not affect the decrease in LC numbers induced by UVB. Despite the differences in effects on LC frequency, both UVA1 and UVB induced an accumulation of DC within lymph nodes draining the site of irradiation. For both irradiation regimens, the accumulation of DC was dependent on IL-1b. This was identified by injecting neutralising IL-1b antibodies before irradiation, which inhibited the accumulation of DC within draining lymph nodes following irradiation. Similar experiments indicated that accumulation of DC following UVB irradiation, but not following UVA1 irradiation, was also dependent upon TNF-a. Induction of cytokines within irradiated skin was examined. UVB exposure increased the expression of IL-10 and TNF-a proteins at the irradiated site. Attempts to identify the source of these cytokines were inconclusive, as both keratinocyte (PAM-212) and melanocyte (B16) cell lines failed to secrete these cytokines following UVB irradiation. Intracellular stores of TNF-a decreased as the dose of radiation increased. The technique of reverse transcription-polymerase chain reaction (RT-PCR) was established to examine expression of cytokine mRNA in irradiated skin. Following UVB irradiation, TNF-a mRNA was upregulated and there was induction of IL-10 mRNA. UVA1 irradiation did not result in such changes. There were also differences in the timecourse of IL-1b mRNA upregulation.