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Antileukotriene agents in the management of asthma

Marc Peters-Golden, MD
Section Editors
Robert A Wood, MD
Bruce S Bochner, MD
Deputy Editor
Helen Hollingsworth, MD


The leukotrienes are proinflammatory mediators produced from arachidonic acid via the 5-lipoxygenase (5-LO) pathway [1,2]. Arachidonic acid is derived from cell membrane phospholipids. Leukotrienes possess diverse biological actions and are increasingly implicated in a variety of disease states [3,4].

Several lines of evidence support the role of leukotrienes in the pathogenesis of asthma, and agents with the capacity to inhibit the synthesis or action of leukotrienes are used in the treatment of asthma.

The use of antileukotriene agents in the management of asthma will be reviewed here. An overview of asthma management and the integrated use of asthma therapies are discussed separately. (See "An overview of asthma management".)


Leukotrienes are synthesized by various leukocytes in response to activation by stimuli such as antigen, microbes, cross-liked immunoglobulin E, complement, osmotic challenge, and certain cytokines [3]. Upon activation, intracellular calcium concentrations rise, causing the enzyme 5-lipoxygenase (5-LO) to translocate from soluble cytosolic or intranuclear pools to the perinuclear membrane. Here, it associates with the helper protein, 5-LO activating protein (FLAP) (figure 1) [3].

FLAP is thought to "present" substrate arachidonate derived from membrane phospholipids to 5-LO, permitting it to catalyze the formation of an unstable intermediate known as leukotriene A4 (LTA4). This intermediate can then be transformed into two different classes of leukotrienes: cysteinyl leukotrienes (CysLTs) and leukotriene B4 (LTB4).


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