leukotriene b-4

Leukotriene B4 (LTB4) is a compound derived from arachidonic acid via the 5-lipoxygenase pathway that mediates certain inflammatory and immune responses. Leukotriene B4 induces neutrophil extracellular traps that impede the clearance of Pneumocystis japonicus.

BIIL-260 hydrochloride is an orally active and highly efficient leukotriene B4 (LTB4) receptor antagonist with anti-inflammatory activity. It interacts with the LTB4 receptor in a saturable, reversible, and competitive manner, inhibiting LTB4-induced intracellular Ca2+ release in human neutrophils.

12-oxo Leukotriene B4 (12-Oxo-LTB4) is a potent pro-inflammatory lipid mediator classified as a dihydroxy fatty acid that is enzymatically derived from arachidonic acid metabolism via the 5-lipoxygenase (5-LO) pathway, and it promotes a diverse array of leukocyte functional responses including cellular aggregation, stimulation of transmembrane ion fluxes, enhancement of lysosomal enzyme release, superoxide anion generation, chemotaxis, and chemokinesis; 12-oxo Leukotriene B4 is an initial oxidative metabolite formed from Leukotriene B4 via the LTB4 12-hydroxydehydrogenase pathway, which undergoes rapid enzymatic conversion first to 10,11-dihydro-12-oxo-LTB4 followed by reduction of the 12-oxo group to yield 10,11-dihydro-LTB4, and this metabolite exhibits significantly reduced biological potency, being approximately 70-fold less potent than LTB4 in stimulating Ca2+ mobilization in human neutrophils (EC50 = 33 nM vs. 0.46 nM) and also markedly less effective at stimulating neutrophil migration (EC50 = 170 nM vs. 2.7 nM).

LTB4 dimethyl amide is a moderate inhibitor of LTB4-induced degranulation of human neutrophils (Ki = 130 nM) and lysozyme release from rat PMNL. LTB4 dimethyl amide appears to be an antagonist of the LTB4 receptor on guinea pig lung membranes.

The effects of Leukotriene B4 (LTB4) are mediated by two known receptors, BLT1 and BLT2. LTB4 is a high affinity ligand for BLT1, and many of its pro-inflammatory effects are believed to be transduced through this receptor. The BLT2 is more enigmatic, in that LTB4 is not a high-affinity ligand, nor is it clear that BLT2 activation promotes inflammation. LTB4 ethanolamide (LTB4-EA) is a theoretical 5-LO metabolite of arachidonoyl ethanolamide (AEA). In CHO cells transfected with human BLTR1, LTB4-EA was a potent antagonist with about three times greater affinity for the receptor than LTB4 (Ki = 1.22 nM versus 3.88 nM). LTB4-EA antagonizes the LTB4-induced contractions of guinea pig lung parenchyma with an EC50 of 10 nM. LTB4-EA thus represents a potential endogenous anti-inflammatory compound functioning as a natural antagonist of BLTR1.

γ-Linolenic acid ethyl ester (Ethyl γ-linolenate) is a leukotriene B4 receptor 4 (LTB4) antagonist with potential anti-inflammatory effects[1].

Hinokiol exhibits anti-inflammatory activity by significantly inhibiting 5-hydroxy-eicosa-tetra-enoic acid (5-HETE) and leukotriene B(4) (LTB4) formations. Additionally, it demonstrates potent activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA).