LTB₄

Leukotriene B4 (LTB4) is a potent pro-inflammatory lipid mediator derived from arachidonic acid via the 5-lipoxygenase (5-LO) pathway^[1][2]. It functions primarily as a chemoattractant for neutrophils, macrophages, and other immune cells, facilitating their migration to sites of tissue injury or infection^[2][3]. Mechanistically, LTB4 binds to two G-protein-coupled receptors, BLT1 and BLT2, which mediate downstream signaling involving MAPKs, PI3K/Akt, and NF-κB activation^[4][5][3]. In disease models, LTB4 contributes to the pathogenesis of inflammatory conditions including rheumatoid arthritis, experimental autoimmune uveitis, atherosclerosis, and chronic neonatal lung injury^[6][7][8][5]. Compared with its high-affinity receptor BLT1, BLT2 exhibits lower affinity for LTB4 and shows tissue-specific expression in keratinocytes and intestinal epithelium^[9][10]. Selective agonists, such as Compound A, activate BLT2 without affecting BLT1, whereas metabolites like 20-hydroxy-LTB4 act as weak agonists but can desensitize neutrophils by downregulating receptor expression^[9][11][3]. Pharmacologic inhibition of LTB4 signaling using receptor antagonists (e.g., BIIL 284) or 5-LO inhibitors (e.g., zileuton) effectively reduces neutrophil recruitment, macrophage influx, and downstream inflammatory responses in preclinical models^[12][8][7]. Therefore, the LTB4-BLT axis represents a mechanistic target for experimental interventions in immune-mediated inflammation and related pathologies^[13].