LTB4

Leukotriene B4 (LTB4) is a potent lipid mediator of inflammation in humans and other mammals. It is a member of the leukotriene family produced from arachidonic acid via the 5-lipoxygenase pathway and is one of the most powerful chemotactic agents for neutrophils.

Biosynthesis of LTB4 begins when inflammatory stimuli activate phospholipase A2, releasing arachidonic acid from membrane phospholipids. The 5-lipoxygenase (5-LO) enzyme, with the 5-LO activating protein (FLAP), converts arachidonic acid to leukotriene A4 (LTA4). LTA4 hydrolase then converts LTA4 to LTB4. LTB4 can be further metabolized to inactive products by various detoxifying enzymes.

LTB4 exerts its effects primarily by signaling through two G protein-coupled receptors: BLT1, which has high affinity for LTB4, and BLT2, with a lower affinity. Through these receptors, LTB4 promotes neutrophil chemotaxis and adhesion, enhances degranulation and respiratory burst, and amplifies inflammatory responses. It plays a role in host defense against infection but can contribute to tissue injury when produced in excess.

Clinical and therapeutic context: Elevated levels of LTB4 have been associated with inflammatory diseases such as asthma, chronic obstructive pulmonary disease, inflammatory bowel disease, rheumatoid arthritis, and psoriasis. Therapeutic approaches include inhibitors of 5-LO or FLAP to reduce leukotriene production and BLT receptor antagonists to block LTB4 signaling. However, clinical efficacy varies and redundancy with other inflammatory mediators often limits outcomes. Drugs like montelukast mainly block LTD4, C4, and LTE4 rather than LTB4.

Metabolism and pharmacology: LTB4 has a short in vivo half-life and is rapidly metabolized to less active products, which are then excreted.