Plitnick L M, Loveless S E, Ladics G S, Holsapple M P, Smialowicz R J, Woolhiser M R, Anderson P K, Smith C, Selgrade M J K
University of North Carolina, Curriculum in Toxicology, Chapel Hill, NC 27599, USA.
Toxicology. 2005 Feb 28;207(3):487-99. doi: 10.1016/j.tox.2004.11.001.
Isocyanates are low-molecular-weight chemicals implicated in allergic asthmatic-type reactions. Identification of chemicals likely to cause asthma is difficult due to the lack of a validated test method. One hypothesis is that differential cytokine induction (Th1 versus Th2 profiles) in the draining lymph node following dermal application can be used to identify asthmagens and distinguish them from contact allergens. In this study, we compared the cytokine mRNA profiles of six chemicals: toluene diisocyanate (TDI), diphenylmethane-4,4'-diisocyanate (MDI), dicyclohexylmethane-4,4'-diisocyanate (HMDI), isophorone diisocyanate (IPDI), p-tolyl(mono)isocyanate (TMI), and meta-tetramethylene xylene diisocyanate (TMXDI). Whereas TDI and MDI are well-known respiratory sensitizers, documentation for HMDI, IPDI, TMI, and TMXDI is limited, but suggests that HMDI and IPDI may have respiratory sensitization potential in humans and TMI and TMXDI do not. Following dermal exposure of BALB/c mice, all six isocyanates induced cytokines characteristic of a Th2 response. Although LLNAs suggested that the doses chosen for the RPA were immunologically equivalent, the isocyanates tested differentiated into two groups, high responders and low responders. However, two of the low responders (TMI and TMXDI) were further tested and induced higher levels of Th2 cytokine message than dinitrochlorobenzene (not an asthmagen). Further study of these chemicals is needed to determine whether the Th2 cytokine responses observed for these low responders is predictive of asthmagenic potential or represents an insufficient signal.
异氰酸酯是与过敏性哮喘样反应有关的低分子量化学物质。由于缺乏经过验证的测试方法，鉴定可能导致哮喘的化学物质很困难。一种假设是，皮肤应用后引流淋巴结中的细胞因子诱导差异（Th1与Th2谱）可用于鉴定哮喘原并将它们与接触性过敏原区分开来。在本研究中，我们比较了六种化学物质的细胞因子mRNA谱：甲苯二异氰酸酯（TDI）、二苯基甲烷-4,4'-二异氰酸酯（MDI）、二环己基甲烷-4,4'-二异氰酸酯（HMDI）、异佛尔酮二异氰酸酯（IPDI）、对甲苯基（单）异氰酸酯（TMI）和间四亚甲基二甲苯二异氰酸酯（TMXDI）。虽然TDI和MDI是众所周知的呼吸道致敏剂，但关于HMDI、IPDI、TMI和TMXDI的文献有限，但表明HMDI和IPDI可能对人类有呼吸道致敏潜力，而TMI和TMXDI则没有。在BALB/c小鼠经皮肤暴露后，所有六种异氰酸酯均诱导出Th2反应特征性的细胞因子。尽管局部淋巴结试验表明为实时定量聚合酶链反应选择的剂量在免疫学上是等效的，但所测试的异氰酸酯分为两组，高反应者和低反应者。然而，对其中两种低反应者（TMI和TMXDI）进行了进一步测试，它们诱导的Th2细胞因子信息水平高于二硝基氯苯（不是哮喘原）。需要对这些化学物质进行进一步研究，以确定观察到的这些低反应者的Th2细胞因子反应是否可预测哮喘原潜力或代表信号不足。
