Pharmaceutical Sciences Department, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73117.
Toxicol Sci. 2019 Mar 1;168(1):179-189. doi: 10.1093/toxsci/kfy289.
Irritant contact dermatitis (ICD), the most common occupational cutaneous illness, is an acute inflammatory response caused by topical irritant exposure. Multiple factors are associated with the manifestation and severity of ICD and contribute to the lack of effective prophylactic and treatment strategies. To determine the pathomechanism of ICD caused by the irritants, benzalkonium chloride (BKC) and JP-8 jet fuel, 2 mouse strains, C57BL/6 and Balb/c, were assessed due to their differential immune predispositions. Dermatitis lesions were obtained for histological examination, cytokine protein expression analysis, and determination of immune cell infiltration via flow cytometric analysis. Following acute (3-day) BKC exposure C57BL/6 skin displayed increased neutrophils and expression of 19 distinct cytokines, but fewer dendritic cells and lower expression of IL-1α and IL-9 as compared with Balb/c skin. Following prolonged (7-day) exposure to BKC, inflammatory cell populations trended similar to 3-day exposure; however, only 6 distinct cytokines were higher in C57BL/6, whereas Balb/c displayed higher expression of IL-27, 28, and 31. Following acute JP-8 exposure, C57BL/6 skin displayed higher levels of γδ T cell infiltration, G and M-CSF expression, but lower populations of neutrophils, monocytes, and dendritic cells compared with Balb/c skin. As with BKC, skin inflammatory cell populations following 7-day JP-8 exposure trended similar to 3-day exposure. However, C57BL/6 skin displayed higher levels of IL-6 and LIF, whereas Balb/c showed increased IL-1β, IL-27, G-CSF, TNFα, and 7 additional chemokines. These findings further define the pathology of ICD, partially explain individual variation of ICD, and offer insight into biomarkers for risk assessment.
刺激性接触性皮炎 (ICD) 是最常见的职业性皮肤病，是由局部刺激性物质暴露引起的急性炎症反应。多种因素与 ICD 的表现和严重程度相关，并导致缺乏有效的预防和治疗策略。为了确定由刺激物引起的 ICD 的发病机制，使用了 2 种不同免疫倾向的小鼠品系，C57BL/6 和 Balb/c，评估了苯扎氯铵 (BKC) 和 JP-8 喷气燃料。通过组织学检查、细胞因子蛋白表达分析以及流式细胞术分析确定免疫细胞浸润，获得了皮炎病变。在急性（3 天）BKC 暴露后，与 Balb/c 皮肤相比，C57BL/6 皮肤显示出增加的中性粒细胞和 19 种不同细胞因子的表达，但树突状细胞较少，IL-1α 和 IL-9 的表达较低。在延长（7 天）暴露于 BKC 后，炎症细胞群与 3 天暴露相似；然而，只有 6 种不同的细胞因子在 C57BL/6 中较高，而 Balb/c 显示出更高的 IL-27、28 和 31 的表达。在急性 JP-8 暴露后，C57BL/6 皮肤显示出更高水平的 γδ T 细胞浸润、G 和 M-CSF 表达，但与 Balb/c 皮肤相比，中性粒细胞、单核细胞和树突状细胞的数量较低。与 BKC 一样，7 天后 JP-8 暴露后的皮肤炎症细胞群与 3 天暴露相似。然而，C57BL/6 皮肤显示出更高水平的 IL-6 和 LIF，而 Balb/c 显示出增加的 IL-1β、IL-27、G-CSF、TNFα 和另外 7 种趋化因子。这些发现进一步定义了 ICD 的病理学，部分解释了 ICD 的个体差异，并为风险评估提供了生物标志物的见解。
