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

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Abstract
Tumour necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) have been implicated in the pathogenesis of asthma. The p38 kinase inhibitor, SB 203580 inhibits TNF-α and IL-1β production in vitro and in vivo. In this study the effect of SB 203580 on allergen-induced airway TNF-α production and inflammatory cell recruitment was investigated in sensitized Brown Norway rats. The allergen-induced increase in bronchoalveolar lavage (BAL) TNF-α 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-α production by 95% without inhibiting either antigen-induced airway eosinophilia or neutrophilia. This data suggests that either the residual TNF-α is sufficent to drive allergen-induced inflammatory cell recruitment into the lung or that TNF-α is not involved in allergen-induced inflammatory cell recruitment.

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