The University of Oklahoma, Health Sciences Center, College of Pharmacy, Department of Pharmaceutical Sciences, Oklahoma City, OK, USA.
J Immunotoxicol. 2013 Apr-Jun;10(2):192-200. doi: 10.3109/1547691X.2012.707700. Epub 2012 Sep 11.
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.
接触性皮炎是与工人赔偿相关的第二大报告职业伤害。炎症细胞因子与皮炎的发展密切相关，其调节可能会加重皮肤损伤，从而导致刺激性增加。IL-6 是一种促炎细胞因子，与皮肤愈合和炎症都有关。为了确定这种多功能细胞因子在化学性刺激性皮炎中的作用，IL-6 缺陷型 (KO)、IL-6 过表达转基因 (TgIL6) 和相应的野生型 (WT) 小鼠分别暴露于丙酮或刺激性 JP-8 喷气燃料或苯扎氯铵 (BKC) 中，每天一次，共 7 天。对暴露皮肤进行组织学分析，并通过 QPCR 和多重 ELISA 分析组织中炎症细胞因子的 mRNA 和蛋白表达模式。结果表明，与 WT 对照和丙酮暴露对照小鼠相比，在 JP-8 暴露后，IL-6KO 小鼠皮肤中 IL-1β、TNFα、CCL2、CCL3 和 CXCL1 的 mRNA 和相应产物蛋白表达显著增加。与丙酮相比，BKC 处理诱导了所有检查细胞因子的表达，而 IL-6KO 小鼠皮肤中的 CCL2 明显更高。组织学分析表明，与 WT 和 TgIL6 小鼠相比，IL-6KO 小鼠在对喷气燃料的反应中显示出明显更多的炎症细胞浸润。分析 M2 巨噬细胞标记物 CD206 的 mRNA 表明，与 WT 相比，用任何一种刺激性物质处理的 IL-6KO 小鼠皮肤中的 CD206 表达降低了 4 倍。综上所述，这些观察结果表明，IL-6 在刺激性皮炎中具有抗炎作用，并且这些作用取决于刺激性物质的化学性质。
