title: The role of interleukin-6 in UVA protection against UVB-induced immunosuppression.
abstract: The proinflammatory cytokine IL-6 is released in the skin following UVB irradiation, but its potential for photoimmune modulation remains unclear. This study utilizes IL-6-deficient mice to demonstrate that IL-6 does not contribute to the normal contact hypersensitivity response, nor to its systemic suppression by UVB radiation or cis-urocanic acid. In contrast, IL-6 was required for the attenuation of UVB- or cis-urocanic acid-induced immunosuppression by sequential or concomitant UVA irradiation. The IL-6 was essential for several reactions previously established to be relevant for UVA photoimmune protection, namely the induction of heme oxygenase-1 (HO-1), the activity of its product carbon monoxide in activating guanylyl cyclase, and the consequent elevation of cutaneous cyclic guanosine monophosphate concentration. In addition, IL-6-deficient mouse skin had an elevated constitutive overexpression of HO activity, apparently not associated with photoimmune protection. This suggested that both the cutaneous level of HO activity, and the receptiveness of the HO-1 gene to stressors like UVA, normally controlled by promoter-binding repressor proteins, may also be under IL-6 control. Thus IL-6 has an important photoimmune protective function through interaction at several levels in the pathway determining the immunologically advantageous actions of UVA radiation. This may constitute a valuable endogenous antiphotocarcinogenic regulatory mechanism.
authors.affiliation: Faculty of Veterinary Science, University of Sydney, Sydney, Australia. v.reeve@vetp.usyd.edu.au
authors.forename: Vivienne E
authors.initials: VE
authors.lastname: Reeve
authors.forename: Rex M
authors.initials: RM
authors.lastname: Tyrrell
authors.forename: Munif
authors.initials: M
authors.lastname: Allanson
authors.forename: Diane
authors.initials: D
authors.lastname: Domanski
authors.forename: Lynette
authors.initials: L
authors.lastname: Blyth
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000737:chemistry / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007107:Immune System / Q000528:radiation effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D014466:Ultraviolet Rays
chemical_list: D007166:Immunosuppressive Agents; D015850:Interleukin-6; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D006152:Cyclic GMP