The effects of ML 3000 on antigen-induced responses in sheep.
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.
Abraham
W M
WM
Division of Pulmonary and Critical Care Medicine, University of Miami at Mount Sinai Medical Center, 4300 Alton Road, Miami Beach, Florida, 33140, USA.
Laufer
S
S
Tries
S
S
D000085:Acetates / Q000494:pharmacology* / Q000627:therapeutic use; D000336:Aerosols; D000818:Animals; D000941:Antigens / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D012756:Sheep
D000085:Acetates; D000336:Aerosols; D000941:Antigens; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011758:Pyrroles; C088092:licofelone