leukotriener

Leukotrienes are a family of lipid inflammatory mediators derived from arachidonic acid. They are produced primarily by leukocytes such as neutrophils, eosinophils, mast cells, and macrophages through the 5-lipoxygenase (5-LOX) pathway with the help of the 5-LOX activating protein (FLAP). The enzymatic sequence forms leukotriene A4 (LTA4), an unstable epoxide, which is then converted to either LTB4 by LTA4 hydrolase or to the cysteinyl leukotrienes LTC4 by LTC synthase; LTC4 is rapidly converted to LTD4 and LTE4 by further enzymatic cleavage.

LTB4 is a potent neutrophil chemoattractant and activator, acting through the BLT1 and BLT2 receptors. The cysteinyl leukotrienes LTC4, LTD4, and LTE4 act mainly on cysteinyl leukotriene receptors CysLT1 and CysLT2, promoting bronchoconstriction, increased vascular permeability, mucus secretion, and recruitment of inflammatory cells.

Clinical relevance of leukotrienes lies in their contribution to inflammatory airway diseases such as asthma and allergic rhinitis. Therapeutic agents include leukotriene receptor antagonists (montelukast, zafirlukast, pranlukast) and a 5-LOX inhibitor (zileuton). Montelukast and related antagonists are used as add-on therapy in mild to moderate asthma and for allergic rhinitis, including pediatric use. Zileuton reduces leukotriene synthesis but requires liver function monitoring due to potential hepatotoxicity; montelukast can rarely be associated with neuropsychiatric effects.

Biomarkers such as urinary LTE4 reflect cysteinyl leukotriene production and are used in research and, to some extent, clinical assessment of inflammatory activity in asthma.