TY - JOUR
T1 - A cytokine cascade including prostaglandin E2, IL-4, and IL-10 is responsible for UV-induced systemic immune suppression
AU - Shreedhar, Vijay
AU - Giese, Todd
AU - Sung, Victor W.
AU - Ullrich, Stephen E.
PY - 1998/4/15
Y1 - 1998/4/15
N2 - Eventhough all of the energy contained with the UV wavelengths of solar 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 laboratories have suggested that one consequence of UV exposure is suppressed Th1 cell activation with normal or enhanced Th2 cell activation, resulting in a shift to a Th2-like phenotype. Cytokines secreted by UV-irradiated keratinocytes, particularly IL-10, have been shown to play a major role in the induction of systemic immune suppression and differential activation of T helper cell subsets. Although IL-10 can influence Th1 cell activation by altering Ag presentation and suppressing IFN-γ secretion, the major signal for the development of a Th2 response is IL-4. Here we tested the hypothesis that UV irradiation induces IL-4 secretion. UV irradiation induced serum IL-4 in a dose-dependent fashion. Injecting UV-irradiated mice with anti. IL-4 blocked immune suppression. We could find no evidence, however, supporting secretion of IL-4 by UV-irradiated keratinocytes. Rather, we suggest that prostaglandins 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 with anti- IL-4 suppressed serum IL-10 levels. In addition, injecting normal mice with PGE2 induced serum IL-4 and IL-10. We suggest that UV expOsure activates a cytokine cascade (PGE2 → IL-4 → IL-10) that ultimately results in systemic immune suppression.
AB - Eventhough all of the energy contained with the UV wavelengths of solar 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 laboratories have suggested that one consequence of UV exposure is suppressed Th1 cell activation with normal or enhanced Th2 cell activation, resulting in a shift to a Th2-like phenotype. Cytokines secreted by UV-irradiated keratinocytes, particularly IL-10, have been shown to play a major role in the induction of systemic immune suppression and differential activation of T helper cell subsets. Although IL-10 can influence Th1 cell activation by altering Ag presentation and suppressing IFN-γ secretion, the major signal for the development of a Th2 response is IL-4. Here we tested the hypothesis that UV irradiation induces IL-4 secretion. UV irradiation induced serum IL-4 in a dose-dependent fashion. Injecting UV-irradiated mice with anti. IL-4 blocked immune suppression. We could find no evidence, however, supporting secretion of IL-4 by UV-irradiated keratinocytes. Rather, we suggest that prostaglandins 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 with anti- IL-4 suppressed serum IL-10 levels. In addition, injecting normal mice with PGE2 induced serum IL-4 and IL-10. We suggest that UV expOsure activates a cytokine cascade (PGE2 → IL-4 → IL-10) that ultimately results in systemic immune suppression.
UR - http://www.scopus.com/inward/record.url?scp=0032522846&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032522846&partnerID=8YFLogxK
M3 - Article
C2 - 9558081
AN - SCOPUS:0032522846
SN - 0022-1767
VL - 160
SP - 3783
EP - 3789
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -