Am. J. Respir. Crit. Care Med., Volume 156, Number 1, July 1997, 11-16

Effects of a Potent Platelet-activating Factor Antagonist, SR27417A, on Allergen-induced Asthmatic Responses

DAVID J. EVANS, PETER J. BARNES, MARC CLUZEL, and BRIAN J. O'CONNOR

Clinical Studies Unit, Royal Brompton Hospital, and Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, United Kingdom; and Sanofi Recherche, Montpellier, France

Platelet-activating factor (PAF) is a lipid-derived mediator that has been implicated in the pathophysiology of airway inflammation in asthma. Its actions include chemotaxis and activation of inflammatory cells, particularly eosinophils. Inhaled PAF causes bronchoconstriction and increased airway responsiveness in human subjects. However, PAF antagonists have so far failed to show benefits in allergen challenge or in the treatment of chronic asthma. SR27417A is a novel PAF antagonist with increased potency compared with previously tested compounds. Twelve asthmatic subjects received treatment with either SR27417A or placebo for 1 wk in a double-blind crossover study. After treatment each subject underwent allergen challenge. Effects were assessed in terms of early and late asthmatic responses and allergen-induced effects on airway responsiveness. Baseline lung function and airway responsiveness were also examined. Treatment with SR27417A significantly attenuated the late asthmatic response (AUC LAR_4-10h: 107 ± 24 after placebo, 79 ± 17 after SR27417A, p < 0.05; mean maximal percent fall in FEV₁ LAR: 29 ± 6% after placebo, 23.5 ± 5.4% after SR27417A, p < 0.05). There were no effects on early asthmatic responses, allergen-induced airway responsiveness, or baseline lung measurements. SR27417A is the most potent PAF antagonist to date, and it has a modest inhibitory effect on the late asthmatic response. This suggests that PAF has a small role in allergic inflammation.

This article has been cited by other articles:

				S. Offer, S. Yedgar, O. Schwob, M. Krimsky, H. Bibi, A. Eliraz, Z. Madar, and D. Shoseyov Negative feedback between secretory and cytosolic phospholipase A2 and their opposing roles in ovalbumin-induced bronchoconstriction in rats Am J Physiol Lung Cell Mol Physiol, March 1, 2005; 288(3): L523 - L529. [Abstract] [Full Text] [PDF]

				P Phipps and C S Garrard The pulmonary physician in critical care * 12: Acute severe asthma in the intensive care unit Thorax, January 1, 2003; 58(1): 81 - 88. [Abstract] [Full Text] [PDF]

				F L Jahnsen, E D Moloney, T Hogan, J W Upham, C M Burke, and P G Holt Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge Thorax, November 1, 2001; 56(11): 823 - 826. [Abstract] [Full Text] [PDF]

				C. Feldman, R. Anderson, A.J. Theron, H.C. Steel, C.E.J. van Rensburg, P.J. Cole, and R. Wilson Vitamin E attenuates the injurious effects of bioactive phospholipids on human ciliated epithelium in vitro Eur. Respir. J., July 1, 2001; 18(1): 122 - 129. [Abstract] [Full Text] [PDF]

				N. R. HENIG, M. L. AITKEN, M. C. LIU, A. S. YU, and W. R. HENDERSON Jr. Effect of Recombinant Human Platelet-activating Factor-Acetylhydrolase on Allergen-induced Asthmatic Responses Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): 523 - 527. [Abstract] [Full Text] [PDF]

				M. A. Giembycz and M. A. Lindsay Pharmacology of the Eosinophil Pharmacol. Rev., June 1, 1999; 51(2): 213 - 340. [Abstract] [Full Text] [PDF]

				P. J. Barnes, K. F. Chung, and C. P. Page Inflammatory Mediators of Asthma: An Update Pharmacol. Rev., December 1, 1998; 50(4): 515 - 596. [Abstract] [Full Text] [PDF]