The mouse ear inflammatory response to topical arachidonic acid.
Application of arachidonic acid (AA) (0.1-4 mg) to the ears of mice produces immediate vasodilatation and erythema (5 min) followed by the abrupt development of edema which is maximal at 40-60 min. The onset of edema coincides with extravasation of protein and leukocytes. After 1 h, the edema begins to wane rapidly and the inflammatory cells leave the tissue so that by 6 h the ears have returned to near normal except for residual erythema. During the period 6-48 h, AA-treated ears show a greatly diminished response with respect to edema and cell infiltrate when AA is applied a second time. Inhibitor studies show that the inflammatory response is due to formation of AA metabolites via both the cyclooxygenase and lipoxygenase pathways. Under appropriate conditions, AA-induced ear edema can be used as a model to screen for compounds showing in vivo lipoxygenase inhibitory activity. Although relatively large doses of AA were applied topically, there was only a modest stimulation of epidermal DNA synthesis and mitotic index with no consequent hyperplasia. Although arachidonic acid is capable of eliciting most aspects of an inflammatory response, the reaction is abrupt in onset and of short duration. Additional factors appear to be required to produce a prolonged inflammatory response with associated tissue destruction, or inflammatory cell activation and immobilization in situ.
D000287:Administration, Topical; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004431:Ear, External / Q000187:drug effects; D004487:Edema / Q000139:chemically induced; D004890:Erythema / Q000139:chemically induced; D005260:Female; D007249:Inflammation / Q000139:chemically induced*; D051379:Mice; D009288:Naproxen / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012867:Skin / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D009288:Naproxen; D004247:DNA; D011451:Prostaglandin-Endoperoxide Synthases