Chai Ok Hee, Lee Hern Ku, Lee Yong Chul, Lee Moo Sam, Han Eui Hyeog, Kim Hyoung Tae, Song Chang Ho
Department of Anatomy, Chonbuk National University, Jeonju, Jeonbuk 561-756, Korea.
Exp Mol Med. 2005 Oct 31;37(5):408-17. doi: 10.1038/emm.2005.51.
Trimellitic anhydride (TMA) is widely used industrially to make epoxy and alkyd resins, plasticizers and surfactants. The purpose of this study was to investigate whether contact hypersensitivity (CHS) is induced by repeated TMA challenge and the role of TNF-alpha and IgE in the TMA-induced CHS. The repetition of the challenge enlarged the extent of an early and a late phase of CHS in TNF-alpha+/+ (B6129SF2/J) and Balb/c mice. In the late phase of TMA-induced CHS, the peak of ear swelling responses by single challenge showed at 24 h after challenge, but the peak was observed at 8 h after repeated challenge. In the TNF-alpha knockout TNF-alpha-/- (B6;129S-Tnftm1Gk1) mice, the repetition of the TMA challenges enlarged the extent of the late phase of CHS, but less than those in TNF-alpha+/+ mice. Injection of anti-TNF-alpha antibody into the peritoneal cavity of Balb/c mice significantly decreased the extent of the late phase of CHS. Subcutaneous injection of anti-IgE antibody into Balb/c mice also decreased the extent of the late phase of CHS in dose-dependent manner. Histologically, infiltration of polymorphonuclear leukocytes and eosinophils was more pronounced in repeatedly TMA-challenged TNF-alpha+/+ and Balb/c mice than in the TNF-alpha-/- mice and anti-TNF-alpha or anti-IgE antibodies treated Balb/c mice. These results indicate that mice sensitized by TMA could possibly offer a useful model to study the mechanism of CHS, and TNF-alpha and IgE may act as potential modulators in the late phase of TMA-induced CHS. Neutralization of TNF-alpha and IgE by anti-TNF-alpha or anti-IgE antibodies may provide therapeutic tools for the treatment of TMA-induced CHS.
偏苯三酸酐（TMA）在工业上广泛用于制造环氧树脂、醇酸树脂、增塑剂和表面活性剂。本研究的目的是调查反复接触TMA是否会诱发接触性超敏反应（CHS），以及肿瘤坏死因子-α（TNF-α）和免疫球蛋白E（IgE）在TMA诱发的CHS中的作用。在TNF-α+/+（B6129SF2/J）和Balb/c小鼠中，反复激发会扩大CHS早期和晚期的范围。在TMA诱发的CHS晚期，单次激发引起的耳部肿胀反应峰值出现在激发后24小时，但反复激发后峰值出现在8小时。在TNF-α基因敲除的TNF-α-/-（B6;129S-Tnftm1Gk1）小鼠中，反复进行TMA激发会扩大CHS晚期的范围，但比TNF-α+/+小鼠的扩大程度小。向Balb/c小鼠腹腔注射抗TNF-α抗体可显著降低CHS晚期的范围。向Balb/c小鼠皮下注射抗IgE抗体也以剂量依赖的方式降低了CHS晚期的范围。组织学上，反复接受TMA激发的TNF-α+/+和Balb/c小鼠中多形核白细胞和嗜酸性粒细胞的浸润比TNF-α-/-小鼠以及接受抗TNF-α或抗IgE抗体治疗的Balb/c小鼠更明显。这些结果表明，由TMA致敏的小鼠可能为研究CHS的机制提供一个有用的模型，并且TNF-α和IgE可能在TMA诱发的CHS晚期作为潜在的调节因子发挥作用。用抗TNF-α或抗IgE抗体中和TNF-α和IgE可能为治疗TMA诱发的CHS提供治疗工具。
