Targeting leukotriene B4 in inflammation

Expert Opin Ther Targets. 2014 Jan;18(1):79-93. doi: 10.1517/14728222.2013.843671. Epub 2013 Oct 4.


Introduction: Leukotriene (LT) B(4) is a powerful proinflammatory lipid mediator and triggers adherence to the endothelium, activates and recruits leukocytes to the site of injury. When formed in excess, LTB(4) plays a pathogenic role and may sustain chronic inflammation in diseases such as asthma, rheumatoid arthritis, and inflammatory bowel disease. Recent investigations have also indicated that LTB(4) is involved in cardiovascular diseases.

Areas covered: As the 5-lipoxygenase pathway involves several discrete, tightly coupled, enzymes, which convert the substrate, 'step by step', into bioactive products, several different strategies have been used to target LTB(4) as a means to treat inflammation. Here, we discuss recent findings regarding the development of selective enzyme inhibitors and antagonists for LTB(4) receptors, as well as their application in preclinical and clinical studies.

Expert opinion: Components of the 5-lipoxygenase pathway have received considerable attention as candidate drug targets resulting in one new class of medications against asthma, that is, the antileukotrienes. However, efforts to specifically target LTB(4) have not yet been fruitful in the clinical setting, in spite of very promising preclinical data. Recently, crystal structures along with hitherto unknown functions of key enzymes in the leukotriene cascade have emerged, offering new opportunities for drug development and, with time, pharmacological intervention in LTB(4)-mediated pathologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonate 5-Lipoxygenase / metabolism
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / enzymology
  • Leukotriene B4 / antagonists & inhibitors*
  • Leukotriene B4 / biosynthesis


  • Leukotriene B4
  • Arachidonate 5-Lipoxygenase