1. ¹Department of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
2. ²Department of Pediatrics and the H.B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA
3. ³Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
4. ⁴Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA
5. ⁵Richard L. Roudebush V.A. Medical Center, Indiana University School of Medicine, Indianapolis, Indiana, USA

Correspondence: Dr Jeffrey B. Travers, H.B. Wells Center for Pediatric Research, James Whitcomb Riley Hospital for Children Room 2659, Indiana University School of Medicine, 702 Barnhill Drive, Indianapolis, Indiana 46202, USA. E-mail: jtravers@iupui.edu

⁶These authors contributed equally to this work.

Received 6 August 2007; Revised 19 November 2007; Accepted 22 November 2007; Published online 17 January 2008.

Abstract

Through its ability to both induce immunosuppression and act as a carcinogen, UVB radiation plays a major role in cutaneous malignancies. Recent studies have indicated that UVB-mediated inhibition of delayed-type hypersensitivity reactions is mediated, in part, by the lipid mediator platelet-activating factor (PAF). The objective of this study was to further define the mechanism by which UVB inhibits contact hypersensitivity (CHS) reactions. UVB irradiation resulted in an inhibition of subsequent CHS to the chemical DNFB in wild-type, but not in PAF-R-deficient mice. UVB-mediated inhibition of CHS was also blocked by a cyclooxygenase-2 (COX-2) inhibitor or a neutralizing antibody directed against IL-10. UVB irradiation upregulated IL-10 mRNA levels in lymph nodes and spleen only to significant levels in PAF-R-expressing mice. Bone marrow transplantation studies demonstrated that UVB-mediated immunomodulatory effects were dependent on PAF-R-positive bone marrow. These studies suggest that UVB irradiation results in epidermal production of PAF agonists, which then act on PAF-R-positive bone marrow-derived cells to upregulate IL-10 through COX-2-generated prostaglandins.