Leukotrienes as mediators of nasal inflammation.
The three sets of studies that we have described support the notion that leukotrienes play a role in the nasal inflammatory response to allergen challenge. Strong inhibition of both leukotrienes and symptoms by A-64077, a trend toward inhibition of both leukotrienes and symptoms by SC-45662, and a lack of effect on either leukotrienes or symptoms by dietary eicosapentaenoic acid provide a consistent association between alterations of leukotrienes and nasal symptoms. A great deal of evidence has now accumulated that leukotrienes are important mediators of inflammation in vivo, but we also know that the chronic stimulus of hay fever produces a much more complex picture than seen in an acute challenge model and that many other mediators such as kinins, other peptides, histamine, and eicosanoids produced outside the 5-lipoxygenase pathway are involved (34,35). Further clinical research will be needed to develop optimal dosing regimens and delivery systems to achieve high concentrations of potent and safe 5-lipoxygenase inhibitors at sites that are critical for producing clinically useful results by modulation of the 5-lipoxygenase pathway.
Knapp
H R
HR
Division of Clinical Pharmacology, University of Iowa, Iowa City 52242-1081, USA.
Murray
J J
JJ
D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D004032:Diet; D006801:Humans; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000502:physiology*; D016859:Lipoxygenase Inhibitors; D012220:Rhinitis / Q000188:drug therapy / Q000276:immunology
D020024:Leukotriene Antagonists; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D001094:Arachidonate 5-Lipoxygenase