Discovery of leukotrienes and development of antileukotriene agents.
OBJECTIVE
This article presents information on the origin of leukotrienes (LTs) and the development of antileukotriene (anti-LT) agents. After reading this article, readers should have an understanding of the chemical mediators involved in the pathogenesis of asthma, the structural features of LTs, and the role of anti-LTs in the management of asthma symptoms.


METHODS
Studies considered relevant and appropriately controlled were used. Only literature in the English language was reviewed.


METHODS
Material was taken from academic/scholarly journals and abstracts.


RESULTS
One of the important chemical mediators implicated in the pathogenesis of asthma is the slow-reacting substance of anaphylaxis, which was subsequently found to comprise LTs C4, D4, and E4. 5-lipoxygenase products from arachidonic acid metabolism, LTs are released from the lung tissue of asthmatic patients and purified human lung mast cells by antigens. The LTs directly induce contraction of bronchial smooth muscle. The use of anti-LT agents, particularly the receptor antagonists zafirlukast and montelukast and the biosynthesis inhibitor zileuton, reverses the bronchoconstrictive effects of LTs and significantly improve asthma symptoms.


CONCLUSIONS
Extensive in vitro and in vivo evidence supports the role of LTs in the pathogenesis of asthma. Their discovery has had a significant impact on treatment strategies, including the use of anti-LT agents, for the management of asthma.
Leff
A R
AR
The University of Chicago, Illinois 60637, USA. aleff@medicine.bsd.uchicago.edu
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D015289:Leukotrienes / Q000032:analysis / Q000502:physiology*; D018077:Receptors, Leukotriene / Q000032:analysis / Q000502:physiology; D013524:Surgical Flaps / Q000502:physiology
D020024:Leukotriene Antagonists; D015289:Leukotrienes; D018077:Receptors, Leukotriene; D001094:Arachidonate 5-Lipoxygenase