Patterson R, Zeiss C R, Harris K E
J Allergy Clin Immunol. 1983 Jun;71(6):604-11. doi: 10.1016/0091-6749(83)90443-8.
Dogs received biweekly or monthly aerosol immunization with single doses of toluene diisocyanate (TDI) that were cumulative doses analogous to human chronic exposure at 0.02 ppm. The three dogs developed systemic immune responses to TDI-dog serum albumin (DSA). The immune responses included IgG, IgA, and IgM antibody responses and development of lymphocyte reactivity. IgA titers approached IgG titers and both were persistent, whereas IgM titers were low and of short duration. IgE antibody titers demonstrated by endpoint cutaneous titration appeared but fluctuated and became negative in spite of continued aerosol exposure of TDI. Immediate-type airway responses occurred after TDI aerosolization. Some limited responses that showed only abnormalities of selected pulmonary function parameters were clearly not immunologically mediated because they occurred with initial exposure. Other immediate-type airway responses occurred that qualitatively simulated IgE-mediated, antigen-induced airway responses in dogs. There was a statistically significant correlation (p = 0.0268) between these latter airway responses and immediate-type skin reactivity. This study demonstrates that this dog model simulates the complexity of airway responses to TDI in man but may provide a laboratory system for evaluation of immunologic or other proposed mechanisms of TDI asthma.
给狗每两周或每月进行一次甲苯二异氰酸酯（TDI）的气溶胶免疫，单次剂量的TDI累积剂量类似于人类在0.02 ppm下的慢性暴露。三只狗对TDI-狗血清白蛋白（DSA）产生了全身免疫反应。免疫反应包括IgG、IgA和IgM抗体反应以及淋巴细胞反应性的发展。IgA滴度接近IgG滴度且两者都持续存在，而IgM滴度较低且持续时间短。通过终点皮肤滴定显示的IgE抗体滴度出现但波动，尽管持续暴露于TDI气溶胶，最终仍变为阴性。TDI雾化后出现速发型气道反应。一些仅表现为选定肺功能参数异常的有限反应显然不是免疫介导的，因为它们在初次暴露时就出现了。还出现了其他速发型气道反应，在质量上模拟了狗体内IgE介导的、抗原诱导的气道反应。这些后一种气道反应与速发型皮肤反应性之间存在统计学上的显著相关性（p = 0.0268）。本研究表明，该狗模型模拟了人类气道对TDI反应的复杂性，但可能为评估TDI哮喘的免疫或其他提出的机制提供一个实验室系统。
