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.