Effect of the p38 kinase inhibitor, SE 203580, on allergic airway inflammation in the rat

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.