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

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.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Bronchial Hyperreactivity / drug therapy*
  • Bronchial Provocation Tests
  • Bronchoalveolar Lavage
  • Cell Movement / drug effects
  • Disease Models, Animal
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Hypersensitivity / drug therapy*
  • Imidazoles / therapeutic use*
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Ovalbumin
  • Pyridines / therapeutic use*
  • Rats
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases


  • Anti-Inflammatory Agents
  • Enzyme Inhibitors
  • Imidazoles
  • Pyridines
  • Tumor Necrosis Factor-alpha
  • Ovalbumin
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580