CysteinylLeukotriene

Cysteinyl leukotrienes (CysLTs) are lipid inflammatory mediators derived from arachidonic acid through the 5-lipoxygenase pathway. The primary cysteinyl leukotrienes are LTC4, LTD4, and LTE4, collectively formed from the intermediate LTA4. LTC4 is produced by LTC4 synthase using glutathione, and LTC4 is subsequently converted to LTD4 and LTE4 by peptidases; all three retain a cysteinyl residue, which distinguishes them from other leukotrienes such as LTB4.

CysLTs are produced by various cells involved in immune and inflammatory responses, including mast cells, eosinophils, basophils, macrophages, and airway epithelial cells. They act locally to amplify inflammation and recruit cells to sites of injury or allergen exposure.

The biological effects of CysLTs are mainly mediated by two G-protein-coupled receptors, CysLT1 and CysLT2. CysLT1 mediates major effects such as bronchoconstriction, increased vascular permeability, mucus secretion, and smooth muscle proliferation. CysLT2 contributes to other inflammatory responses and may modulate the activity of CysLT1. These mediators play a well-established role in the pathophysiology of asthma and allergic rhinitis.

Pharmacology and clinical use focus on antagonism of the CysLT1 receptor. Montelukast, zafirlukast, and pranlukast are selective CysLT1 antagonists used as add-on therapy for mild-to-moderate persistent asthma and for exercise-induced bronchoconstriction, as well as in allergic rhinitis. In addition to treatment, suppression of CysLT signaling can reduce airway hyperresponsiveness and leukotriene-mediated inflammation. Rare adverse effects can include neuropsychiatric symptoms with some agents. LTE4 levels in urine can serve as a biomarker of CysLT activity.