Holliday M R, Corsini E, Smith S, Basketter D A, Dearman R J, Kimber I
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
Am J Contact Dermat. 1997 Sep;8(3):158-64.
Increasing evidence shows that contact allergens and skin irritants can induce or upregulate the cutaneous expression of cytokines, including those that are required for the initiation of immune responses and which participate in inflammatory reactions.
The present investigation compared the ability of the skin allergens oxazolone and 2,4-dinitrochlorobenzene (DNCB) and the skin irritant benzalkonium chloride (BZC) to stimulate the cutaneous expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in mice.
Each chemical tested induced the dose-dependent production of IL-6 with similar kinetic profiles. BZC was less effective at provoking increases in this cytokine; concentrations (1%) that caused marked edema failed to stimulate significant changes in IL-6 expression. Under conditions of topical exposure in which each of these chemicals caused a vigorous inflammatory response in the skin, as measured by induced edema and the increased production of IL-6, only oxazolone and DNCB stimulated expression of TNF-alpha. The failure of BZC to initiate TNF-alpha production in the skin was not attributable to inhibition of the bioassay used to measure this cytokine and was apparently independent of the stimulation by this chemical of TNF-alpha inhibitory factors.
These data indicate that not all chemicals that have the ability to cause skin irritation and cutaneous inflammation will elicit detectable TNF-alpha responses and that characterization of cutaneous irritants and allergens on the basis of induced cytokine expression patterns in the skin must be approached with caution.
越来越多的证据表明，接触性变应原和皮肤刺激物可诱导或上调细胞因子在皮肤中的表达，包括那些启动免疫反应和参与炎症反应所需的细胞因子。
本研究比较了皮肤变应原恶唑酮和2,4-二硝基氯苯（DNCB）以及皮肤刺激剂苯扎氯铵（BZC）刺激小鼠皮肤中白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）表达的能力。
每种受试化学物质均以相似的动力学曲线诱导IL-6的剂量依赖性产生。BZC在引发这种细胞因子增加方面效果较差；导致明显水肿的浓度（1%）未能刺激IL-6表达发生显著变化。在局部暴露条件下，这些化学物质中的每一种都会在皮肤中引起强烈的炎症反应，通过诱导水肿和IL-6产生增加来衡量，只有恶唑酮和DNCB刺激TNF-α的表达。BZC未能在皮肤中引发TNF-α产生并非归因于用于测量该细胞因子的生物测定法受到抑制，并且显然与该化学物质对TNF-α抑制因子的刺激无关。
这些数据表明，并非所有具有引起皮肤刺激和皮肤炎症能力的化学物质都会引发可检测到的TNF-α反应，并且基于皮肤中诱导的细胞因子表达模式对皮肤刺激物和变应原进行表征时必须谨慎。
