ARACHIDONIC-ACID METABOLITES - MEDIATORS OF INFLAMMATION IN ASTHMA

Asthma is increasingly recognized as a mediator-driven inflammatory pr ocess in the lungs. The leukotrienes (LTs) and prostaglandins (PGs), t wo families of proinflammatory mediators arising via arachidonic acid metabolism, have been implicated in the inflammatory cascade that occu rs in asthmatic airways. The PG pathway normally maintains a balance i n the airways; both PGD(2) and thromboxane A(2) are bronchoconstrictor s, whereas PGE(2) and prostacyclin are bronchoprotective. The actions of the LTs, however, appear to be exclusively proinflammatory in natur e. The dihydroxy-LT, LTB(4), may play an important role in attracting neutrophils and eosinophils into the airways, whereas the sulfidopepti de leukotrienes (LTC(4), LTD(4), and LTE(4)) produce effects that are characteristic of asthma, such as potent bronchoconstriction, increase d endothelial membrane permeability leading to airway edema, and enhan ced secretion of thick, viscous mucus. Given the significant role of t he inflammatory process in asthma, newer pharmacologic agents, such as the sulfidopeptide-LT antagonists, zafirlukast, montelukast, and pran lukast and the 5-lipoxygenase (5-LO) inhibitor, zileuton, have been de veloped with the goal of targeting specific elements of the inflammato ry cascade. These drugs appear to represent improvements to the existi ng therapeutic armamentarium. In addition, the results of clinical tri als with these agents have helped to expand our understanding of the p athogenesis of asthma.