Abstract
Leukotriene B4 (LTB4) is a lipid inflammatory mediator derived from membrane phospholipids by the sequential actions of cytosolic phospholipase A2 (PLA2), 5-lipoxygenase (5-LO) and leukotriene A4 (LTA4) hydrolase. Several inflammatory diseases, including asthma, chronic obstructive pulmonary disease, arthritis and inflammatory bowel disease, have been associated with elevated levels of LTB4. As a result, pharmacological strategies to modulate the synthesis of LTB4 (inhibition of PLA2, 5-LO or LTA4 hydrolase) or the effects of LTB4 itself (antagonism of LTB4 receptors) are being developed by several companies. Two G-protein-coupled receptors mediate the effects of LTB4, namely BLT1 and BLT2. The pharmacology, expression and function of these two receptors were last reviewed by Tager and Luster in 2004. Since then, there has been an increased understanding of the function of these receptors, in particular for the lesser understood of the two receptors, BLT2. Furthermore, since last reviewed in 1996, there have been several clinical developments in the use of BLT receptor antagonists for inflammatory diseases. This review summarizes the latest preclinical and clinical developments in BLT antagonism for inflammatory diseases and discusses potential future developments.
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