Effect of the p38 kinase inhibitor, SE 203580, on allergic airway inflammation in the rat
Effect of the p38 kinase inhibitor, SE 203580, on allergic airway inflammation in the rat
复制标题
DOI：
10.1038/sj.bjp.0703605
复制
发表时间：
2000-09-01
影响因子：
7.3
通讯作者：
Sargent, CA
中科院分区：
文献类型：
--
作者：
Escott, KJ;Belvisi, MG;Sargent, CA
肿瘤坏死因子- α (tnf - α)和白细胞介素-1 β (IL-1 β)与哮喘的发病机制有关。p38激酶抑制剂SE 203580在体内和体外均可抑制tnf - α和IL-1 β的产生。本研究在致敏的褐挪威大鼠中研究了SE 203580对变应原诱导的气道TNF-a产生和炎症细胞募集的影响。SE 203580在每个剂量（10-100 mg kg(-1), p.o）均可抑制过敏原诱导的支气管肺泡灌洗（BAL） tnf - α升高。相比之下，SE 203580 （10-100 mg kg(-1), p.o）对卵清蛋白诱导的嗜酸性粒细胞和中性粒细胞均无抑制作用。总之，SE 203580抑制BAL tnf - α产生95%，而不抑制抗原诱导的气道嗜酸性粒细胞或嗜中性粒细胞。这些数据表明，要么残留的tnf - α足以驱动过敏原诱导的炎症细胞募集进入肺部，要么tnf - α不参与过敏原诱导的炎症细胞募集。
Tumour necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) have been implicated in the pathogenesis of asthma. The p38 kinase inhibitor, SE 203580 inhibits TNF-alpha and IL-1 beta production in vitro and in vivo. In this study the effect of SE 203580 on allergen-induced airway TNF-a production and inflammatory cell recruitment was investigated in sensitized Brown Norway rats. The allergen-induced increase in bronchoalveolar lavage (BAL) TNF-alpha was inhibited by SE 203580 at every dose tested (10-100 mg kg(-1), p.o.). In contrast, neither ovalbumin-induced eosinophilia or neutrophilia were inhibited by SE 203580 (10-100 mg kg(-1), p.o.). In conclusion, SE 203580 inhibits BAL TNF-alpha production by 95% without inhibiting either antigen-induced airway eosinophilia or neutrophilia. This data suggests that either the residual TNF-alpha is sufficent to drive allergen-induced inflammatory cell recruitment into the lung or that TNF-alpha is not involved in allergen-induced inflammatory cell recruitment.