Moderating the inflammation of asthma: inhibiting the production or action of products of the 5-lipoxygenase pathway.
The products of the 5-lipoxygenase pathway of arachidonic acid metabolism, particularly the leukotrienes, can mediate bronchoconstriction, mucous secretion, airway mucosal edema, chemotaxis, and mobilization of cells into the airway in the inflammatory process of asthma. This paper will review the current data on the efficacy of available leukotriene antagonists or inhibitors that act on the 5-lipoxygenase pathway in induced bronchoconstriction in humans and in clinical studies in asthma. Studies of asthmatic responses to antigen and cold air hyperventilation and exercise will be discussed. Data will be reviewed from investigations regarding the effects of these pharmacological agents as they relate to increased airway tone in asthmatic patients and, finally, as they relate to clinical and physiological improvement in mild to moderate asthma. These studies suggest that the antagonists and inhibitors that affect the 5-lipoxygenase products of arachidonic acid may provide a new approach in the pharmacologic treatment of asthma. Further clinical studies will be required to define the precise role of these agents.
Israel
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Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts.
D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology*; D001095:Arachidonic Acids / Q000378:metabolism; D001249:Asthma / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology* / Q000517:prevention & control*
D001095:Arachidonic Acids; D001094:Arachidonate 5-Lipoxygenase