Sulfidopeptide-leukotrienes are major mediators of arachinodic acid-induced mouse ear edema

Abstract

The inflammatory response of the mouse ear to topical application of arachidonic acid (2 mg/ear) was examined to study the roles of sulfidopeptide-leukotrienes (LTs) and prostaglandin (PG) E 2 as mediators of edema. The increases in ear thickness caused by arachidonc acid (AA)_(edema), reached a maximum at 45 to 60 min after AA application. The amounts of immunoreactive LTC 4 and immunoreactive PGE 2 produced increased significantly in 5 to 10 min, and then diminished gradually over 60 min. 5-lipoxygenase inhibitors, dual cyclooxygenase/lipoxygenase inhibitors and anti-histamines significantly inhibited AA-induced ear edema. Both production of PGE 2 and LTC 4 were suppressed by NDGA at 1 mg/ear which also inhibited ear swelling. However aspirin, which enhanced LTC 4 production in AA-induced ear edema did not inhibit the ear swelling. Hypodermic injection of LTC 4 at 25 ng or PGE 2 at 500 ng/ear did not cause swelling, but edeman was induced when both compounds were injected simultaneously. Moreover ear swelling was induced by injection of both LTD 4 at 50 ng and PGE 2 at 500 ng/ear. Furthermore, concomitant injection of histamine at 500 ng or serotonin at 50 ng/ear with LTC 4 at 25 ng caused ear swelling but both compounds at the same dose alone did not induce swelling. These results suggest that AA-induced ear edema is predominantly mediated by LTC 4 and other lipoxygenase products while PGE 2 (in the presence of LTs) acts to facilitated ear swelling, although serotonin and histamine may also contribute.