Title: Targeting Leukotrienes for the Treatment of COPD?
Volume: 8
Issue: 4
Author(s): Panagis Drakatos, Dimosthenis Lykouras, Fotis Sampsonas, Kiriakos Karkoulias and Kostas Spiropoulos
Affiliation:
Keywords:
Antileukotriene agents cysteinyl leukotrienes, LTB 4, montelukast, zafirlukast, pranlukast, zileuton, 5-lipoxygenase, activating protein inhibitors
Abstract: New drugs and new approaches of the treatment of chronic obstructive pulmonary disease (COPD) are needed. Despite recent advances in medical therapeutics, treatment of patients with COPD remains largely symptomatic. Although inhaled corticosteroids are currently the drug of choice for anti-inflammatory therapy, the inflammatory process in COPD is essentially steroid resistant. By now, COPD has been increasingly recognized as an inflammatory disease characterized by sputum neutrophilia and, in some cases, eosinophilia. Moreover other cell types thought to play the predominant role in COPD, are cytotoxic T lymphocytes (CD8+ T) cells and machrophages. Leukotriene B4, (LTB 4), a neutrophil and T cell chemoattractant which is produced by machrophages, neurophils and epithelial cells, is a potent inflammatory mediator. Also cysteinyl leukotrienes (LTC4, LTD4 and LTE4) are known to induce mucus secretion, inflammatory cell infiltration, increase vascular permeability and tissue edema, damage ciliary clirens, and cause severe bronchoconstriction. These are derivatives of arachidonic acid, metabolized via 5-lypoxygenase (5-LO) pathway. There are several sites along this pathway that antileukotriene agents exert their action and at the end-organ receptors. They are classified into two major categories: receptor antagonists and synthesis inhibitors. Beneficial effects on therapy of patients with COPD have already derived from studies, while they seem well tolerated. More studies are underway.
