Escott K J, Belvisi M G, Birrell M A, Webber S E, Foster M L, Sargent C A
Department of Pharmacology, Aventis Pharmaceuticals, Rainham Road South, Dagenham, Essex, RM10 7XS.
Br J Pharmacol. 2000 Sep;131(2):173-6. doi: 10.1038/sj.bjp.0703605.
Tumour necrosis factor-alpha (TNF-alpha) and interleukin 1beta (IL-1beta) have been implicated in the pathogenesis of asthma. The p38 kinase inhibitor, SB 203580 inhibits TNF-alpha and IL-1beta production in vitro and in vivo. In this study the effect of SB 203580 on allergen-induced airway TNF-alpha 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 SB 203580 at every dose tested (10 - 100 mg kg(-1), p.o.). In contrast, neither ovalbumin-induced eosinophilia or neutrophilia were inhibited by SB 203580 (10 - 100 mg kg(-1), p.o.). In conclusion, SB 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 sufficient to drive allergen-induced inflammatory cell recruitment into the lung or that TNF-alpha is not involved in allergen-induced inflammatory cell recruitment.
肿瘤坏死因子-α（TNF-α）和白细胞介素1β（IL-1β）与哮喘的发病机制有关。p38激酶抑制剂SB 203580在体内外均可抑制TNF-α和IL-1β的产生。在本研究中，在致敏的棕色挪威大鼠中研究了SB 203580对变应原诱导的气道TNF-α产生和炎性细胞募集的影响。在每个测试剂量（10 - 100 mg kg(-1)，口服）下，SB 203580均可抑制变应原诱导的支气管肺泡灌洗（BAL）中TNF-α的增加。相比之下，SB 203580（10 - 100 mg kg(-1)，口服）对卵清蛋白诱导的嗜酸性粒细胞增多或中性粒细胞增多均无抑制作用。总之，SB 203580可抑制BAL中TNF-α的产生达95%，而不抑制抗原诱导的气道嗜酸性粒细胞增多或中性粒细胞增多。该数据表明，要么残余的TNF-α足以驱动变应原诱导的炎性细胞募集到肺中，要么TNF-α不参与变应原诱导的炎性细胞募集。
