The effects of ML 3000 on antigen-induced responses in sheep

W. M. Abraham, S. Laufer, S. Tries

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

ML 3000 is a dual inhibitor of cyclooxygenase (COX) and 5-lipoxygenase (5-LO), two enzymes that contribute to the airway inflammation in asthma. When administered as an aerosol at a dose of 100 mg, 0.5 h before antigen challenge in allergic sheep, ML 3000 provided significant inhibition against the early bronchial response (EAR, mean 33% protection, P < 0.05), completely blocked the late antigen-induced bronchoconstriction (LAR, mean 81% protection, P < 0.05) and the airway hyperresponsiveness (AHR, P < 0.05) to aerosolized carbachol that occurs 24 h after antigen challenge in this model. Consistent with this functional protection was a small but significant reduction in the percentage of neutrophils recovered in bronchoalveolar lavage (BAL) at 8 h and 24 h after challenge. These findings are similar to previous data obtained in this animal model with other 5-LO inhibitors (blockade of the LAR and AHR) and COX inhibitors (blockade of AHR). These results suggest that aerosol administration of a dual inhibitor of COX and 5-LO may have beneficial effects in the treatment of allergic airway disease.

Original languageEnglish (US)
Pages (from-to)167-173
Number of pages7
JournalPulmonary Pharmacology and Therapeutics
Volume10
Issue number3
DOIs
StatePublished - Jun 1997

Keywords

  • 5-lipoxygenase
  • Asthma
  • Bronchoconstriction
  • Cyclooxygenase
  • Late response
  • Therapy

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmacology

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