Leukotriene generation and clinical implications.
Since the elucidation of the structure of the cysteinyl leukotrienes (LTs) > 20 years ago, considerable progress has been made in our understanding of the role of these molecules in health and disease, particularly regarding bronchial asthma. This study will review the biochemistry of the 5-lipoxygenase pathway for LT generation. It will discuss the early evidence that LTs, the cysteinyl LTs in particular, have the biological properties expected for molecules that participate in the pathogenesis of bronchial asthma and the evidence for their formation in the airways of asthmatic individuals. It will briefly review tile evidence that LT-modifying drugs are effective in the management of bronchial asthma and will discuss novel developments in our understanding of the proinflammatory properties of the LTs including their role as autocrine mediators of leukocyte responses. The pharmacogenomics of 5-lipoxgenase and LTC4 synthase in bronchial asthma will be discussed.
Arm
Jonathan P
JP
Department of Medicine, Harvard Medical School, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use; D015289:Leukotrienes / Q000378:metabolism / Q000502:physiology*; D018077:Receptors, Leukotriene / Q000627:therapeutic use; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
D018927:Anti-Asthmatic Agents; D016207:Cytokines; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D018077:Receptors, Leukotriene