Pulmonary diseases other than asthma as potential targets for antileukotriene therapy
- 41 Downloads
A highly plausible rationale exists for implicating LTs in the pathogenesis of all the diseases considered in this discussion. In general, the weakest link is the paucity of therapeutic trials in humans. It is only recently that pharmacologic agents with acceptable potency and specificity have been available. As experience and comfort with these new anti-LT agents grow, it is anticipated that their application will be extended beyond asthma to the diseases discussed herein. For most of these diseases, a case can be made for the involvement of not only cysteinyl LTs, but also of LTB4 and 5-HETE. For this reason, it can be hypothesized that drugs that inhibit 5-LO metabolism at a proximal step (i.e., 5-LO or 5-LO activating protein) would appear to hold the most promise and versatility. It is hoped that the opportunity to test this hypothesis will be realized.
KeywordsChronic Obstructive Pulmonary Disease Cystic Fibrosis Pulmonary Hypertension Alveolar Macrophage Idiopathic Pulmonary Fibrosis
Unable to display preview. Download preview PDF.
- 6.Shindo K, Hirai Y, Fukumura M, Koide K. Plasma levels of leukotriene E4 during clinical course of chronic obstructive pulmonary disease. Prostaglandins 1997;56:213–217.Google Scholar
- 9.Sampson A, Spencer D, Green C, Piper P, Price J. Leukotrienes in the sputum and urine of cystic fibrosis children. Brit J Clin Pharmacol 1990;30:861–869.Google Scholar
- 14.Oda H, Kadota J, Kohno S, Hara K. Leukotriene B4 in bronchoalveolar lavage fluid with diffuse panbronchiolitis. Chest 1995;108:115–122.Google Scholar
- 15.Seeger W, Grimminger F, Barden M, Becker G, Lohmeyer J, Heinrich D, Lasch H. Omega-oxidized leukotriene B4 deteced in the broncho-alveolar lavage fluid of patients with noncardiogenic pulmonary edema, but not in those with cardiogenic edema. Intensive Care Med 1991;17:1–6.PubMedCrossRefGoogle Scholar
- 16.Antonelli M, Raponi G, Lenti L, Severi L, Capelli O, Riccioni L, De Blasi R, Conti G, Mancini C. Leukotrienes and alpha tumor necrosis factor levels in the bronchoalveolar lavage fluid of patient at risk for the adult, respiratory distress syndrome. Minerva Anestesiol 1994;60:419–426.PubMedGoogle Scholar
- 17.Antonelli M, Bufi M, De Blasi R, Crim G, Conti G, Mattia C, Vivino G, Lenti L, Lombardi D, Dotta A, Pontieri G, Gasparetto A. Detection of leukotrienes B4, C4 and of their isomers in arterial, mixed venous blood and bronchoalveolar lavage fluid from ARDS patients. Intensive Care Med 1989;15:296–301.PubMedGoogle Scholar
- 25.Coggeshall J, Christman B, Lefferts P, Serafin W, Blair I, Butterfield M, Snapper J. Effect of inhibition of 5-lipoxygenase metabolism of arachidonic acid on response to endotoxemia in sheep. J Appl Physiol 1998;65:1351–1359.Google Scholar
- 27.Wollert, P, Menconi M, O’Sullivan B, Larkin V, Wang H, Larkin V, Fink M. LY255283, a novel leukotriene B4 receptor antagonist, limits activation of neutrophils and prevents acute lung injury induced by endotoxin in pigs. 1993;114:191–198.Google Scholar
- 38.Peters-Golden M, McNish R, Davis J, Blackwood R, Brock T. Colchicine inhibits arachidonate release and 5-lipoxygenase action in alveolar macrophages. Am J Physiol (Lung Cell Mol Physiol) 1996;271:L1004-L1013.Google Scholar
- 44.Tabata T, Ono S, Song C, Noda M, Suzuki S, Tanita T, Fujimura S. Role of leukotriene B4 in monocrotaline-induced pulmonary hypertension. Jap J Thorac Dis 1997;35:160–166.Google Scholar