Targeting leukotriene B₄ in inflammation

Abstract

Introduction: Leukotriene (LT) B₄ 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, LTB₄ 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 LTB₄ 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 LTB₄ as a means to treat inflammation. Here, we discuss recent findings regarding the development of selective enzyme inhibitors and antagonists for LTB₄ 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 LTB₄ 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 LTB₄-mediated pathologies.

Keywords::

• 5-lipoxygenase
• arachidonic acid
• inflammatory diseases
• leukotriene A₄ hydrolase

Notes

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