title: IL-6 deficiency exacerbates skin inflammation in a murine model of irritant dermatitis.
abstract: Contact dermatitis is the second most reported occupational injury associated with workers compensation. Inflammatory cytokines are closely involved with the development of dermatitis, and their modulation could exacerbate skin damage, thus contributing to increased irritancy. IL-6 is a pro-inflammatory cytokine paradoxically associated with both skin healing and inflammation. To determine what role this pleiotropic cytokine plays in chemically-induced irritant dermatitis, IL-6 deficient (KO), IL-6 over-expressing transgenic (TgIL6), and corresponding wild-type (WT) mice were exposed to acetone or the irritants JP-8 jet fuel or benzalkonium chloride (BKC) daily for 7 days. Histological analysis of exposed skin was performed, as was tissue mRNA and protein expression patterns of inflammatory cytokines via QPCR and multiplex ELISA. The results indicated that, following JP-8 exposure, IL-6KO mice had greatly increased skin IL-1β, TNFα, CCL2, CCL3, and CXCL1 mRNA and corresponding product protein expression when compared to that of samples from WT counterparts and acetone-exposed control mice. BKC treatment induced the expression of all cytokines examined as compared to acetone, with CCL2 significantly higher in skin from IL-6KO mice. Histological analysis showed that IL-6KO mice displayed significantly more inflammatory cell infiltration as compared to WT and TgIL6 mice in response to jet fuel. Analysis of mRNA for the M2 macrophage marker CD206 indicated a 4-fold decrease in skin of IL-6KO mice treated with either irritant as compared to WT. Taken together, these observations suggest that IL-6 acts in an anti-inflammatory manner during irritant dermatitis, and these effects are dependent on the chemical nature of the irritant.
authors.affiliation: The University of Oklahoma, Health Sciences Center, College of Pharmacy, Department of Pharmaceutical Sciences, Oklahoma City, OK, USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Lee
authors.forename: Bethany M
authors.initials: BM
authors.lastname: Mickle-Kawar
authors.forename: Randle M
authors.initials: RM
authors.lastname: Gallucci
mesh_terms: D000096:Acetone / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D001548:Benzalkonium Compounds / Q000008:administration & dosage / Q000009:adverse effects; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D017453:Dermatitis, Irritant / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D006838:Hydrocarbons / Q000008:administration & dosage / Q000009:adverse effects; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
chemical_list: D001548:Benzalkonium Compounds; D018925:Chemokines; D016207:Cytokines; D006838:Hydrocarbons; D015850:Interleukin-6; C098607:JP8 aviation fuel; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D000096:Acetone