Current state and future prospect of the therapeutic strategy targeting cysteinyl leukotriene metabolism in asthma.
Current state and future prospect of the therapeutic strategy targeting cysteinyl leukotriene metabolism in asthma
Asthma is an allergic disorder with dominant type 2 airway inflammation, and its prevalence is increasing worldwide. Inhalation of corticosteroids is the primary treatment for asthma along with add-on drugs, including long-acting β2 agonists and/or cysteinyl leukotriene (cys-LT) receptor antagonists, in patients with poorly controlled asthma. Cys-LTs are composed of leukotriene C4 (LTC4), LTD4, and LTE4, which are enzymatically metabolized from arachidonic acid. These molecules act as inflammatory mediators through different types of high-affinity receptors, namely, CysLT1, CysLT2, and CysLT3 (also named as GPR99). CysLT1 antagonists possessing anti-inflammatory and bronchodilatory effects can be orally administered to patients with asthma. Recently, molecular biology-based studies have revealed the mechanism of inflammatory responses via other receptors, such as CysLT2 and CysLT3, as well as the importance of upstream inflammatory regulators, including type 2 cytokines (e.g., interleukins 4 and 5), in controlling cys-LT metabolism. These findings indicate the therapeutic potential of pharmacological agents targeting cys-LT metabolism-related receptors and enzymes, and antibody drugs neutralizing or antagonizing type 2 cytokines. This review focuses on the current state and future prospect of the therapeutic strategy targeting cys-LT metabolism.