Effect of the 5-lipoxygenase inhibitor, fenleuton, on antigen-induced neutrophil accumulation and lung function changes in horses with chronic obstructive pulmonary disease.
The leukotrienes (LT) LTD4 and LTB4 have been shown to cause bronchoconstriction and neutrophil accumulation, respectively, in horse lungs. Such changes are characteristic of the equine allergic respiratory disease, chronic obstructive pulmonary disease (COPD). To further investigate the role of these putative mediators in the pathogenesis of equine COPD the effect of a 5-lipoxygenase inhibitor, fenleuton, on antigen-induced changes in horses with this condition has been examined. Six horses with COPD underwent a series of four antigen challenges, one month apart, with placebo pre-treatment on three occasions and fenleuton (4 days oral dosing 5 mg/kg) pre-treatment on one occasion. Three horses received fenleuton prior to the second challenge and three horses received the drug prior to the fourth antigen challenge. Changes in radiolabelled neutrophil distribution, lung function and peripheral leucocyte counts were monitored on each occasion for 7 h following the start of antigen challenge. Antigen challenge caused an increase in radioactive counts over the lungs and a decrease in peripheral leucocyte count. Neither response was affected by fenleuton pre-treatment. Mean maximal changes in pleural pressure (delta Pplmax) and respiratory rate were also unaffected by fenleuton pre-treatment. However, in the two horses which responded to antigen-challenge with a particularly marked increase in delta Pplmax (> 15 cm H2O), prior administration of fenleuton reduced the response by 64 and 63%. These results suggest that 5-lipoxygenase inhibitors warrant further investigation as bronchodilators in equine COPD.
Department of Veterinary Basic Sciences, Royal Veterinary College, North Mymms, Hertfordshire, UK.
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D000818:Animals; D000941:Antigens; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006734:Horse Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006736:Horses; D006918:Hydroxyurea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007958:Leukocyte Count / Q000662:veterinary; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008173:Lung Diseases, Obstructive / Q000662:veterinary*; D008297:Male; D009504:Neutrophils / Q000187:drug effects*
D000941:Antigens; D001993:Bronchodilator Agents; D016859:Lipoxygenase Inhibitors; C109612:fenleuton; D006918:Hydroxyurea