A CYTOKINE CASCADE INCLUDING PROSTAGLANDIN E-2, IL-4, AND IL-10 IS RESPONSIBLE FOR UV-INDUCED SYSTEMIC IMMUNE SUPPRESSION

Even though all of the energy contained with the UV wavelengths of sol ar radiation is absorbed within the epidermis and upper layers of the dermis, UV irradiation can suppress immune responses to Ag introduced at distant nonirradiated sites, In addition, data from a number of lab oratories have suggested that one consequence of UV exposure is suppre ssed Th1 cell activation with normal or enhanced Th2 cell activation, resulting in a shift to a Th2-like phenotype, Cytokines secreted by UV -irradiated keratinoctyes, particularly IL-IO, have been shown to play a major role in the induction of systemic immune suppression and diff erential activation of T helper cell subsets, Although IL-IO can influ ence Th1 cell activation by altering Ag presentation and suppressing I FN-gamma secretion, the major signal for the development of a Th2 resp onse is IL-4. Here we tested the hypothesis that UV irradiation induce s IL-4 secretion, UV irradiation induced serum IL-4 in a dose-dependen t fashion, Injecting UV-irradiated mice with anti-IL-4 blacked immune suppression. We could find no evidence, however, supporting secretion of IL-4 by UV-irradiated keratinocytes. Rather, we suggest that prosta glandins released by irradiated keratinocytes induce serum IL-4 since treating UV-irradiated mice with a cyclooxygenase-2 inhibitor blocked its production, Moreover, we found that treating UV-irradiated mice wi th anti-IL-4 suppressed serum IL-10 levels, In addition, injecting nor mal mice with PGE(2) induced serum IL-4 and IL-10,We suggest that UV e xposure activates a cytokine cascade (PGE(2)-->IL-4 --> IL-10) that ul timately results in systemic immune suppression.