The role of eicosanoids in respiratory mucus hypersecretion.

The role of eicosanoids in the excessive secretion of respiratory mucous glycoproteins (MGP) accompanying immediate hypersensitivity and inflammatory pulmonary states has only been addressed in the last few years. Three lines of evidence suggest that eicosanoids may participate in the physiologic regulation of MGP secretion as well as being capable of stimulating increased MGP production. First, inhibition of eicosanoid generation with corticosteroids or eicosatetraynoic acid (ETYA) reduces ongoing baseline MGP secretion while selective inhibition of prostaglandin production with nonsteroidal anti-inflammatory agents increases MGP release. Second, arachidonic acid and a variety of eicosanoids stimulate MGP secretion in vitro. In fact, several lipoxygenase pathway metabolites including hydroxyeicosatetraenoic acids (HETEs) and leukotrienes (LTC4 and LTD4) significantly increase MGP secretion in nanogram quantities. Third, a variety of pulmonary cells including airway epithelium, endothelial cells, mast cells, alveolar macrophages and neutrophilic leukocytes generate eicosanoids under conditions that would be encountered in clinical states in which mucus secretion occurs. Thus, mucus secretion during both normal and stimulated states would be influenced by eicosanoids. It seems likely that this eicosanoid-mucus secretion relationship is very important in all forms of asthma, but most particularly in aspirin-related asthma.