Experimental Otitis Media with Effusion Induced by Platelet Activating Factor

Abstract

This study tested the hypothesis that platelet activating factor (PAF) in the middle ear can induce otitis media with effusion (OME) and that PAF antagonists can prevent PAF-induced OME. An initial trial of 16 micrograms of PAF was injected into chinchilla bullae, and all ears developed middle ear effusion (MEE) within 48 hours. Subsequent trials were performed to test dose dependency. Interestingly, 1 or 16 micrograms of PAF caused more MEE and inflammation than did 4 or 8 micrograms. A dose of 0.5 micrograms PAF did not cause MEE. Middle ear effusion from injected bullae contained the full spectrum of lipoxygenase and cyclooxygenase products; additionally, more PAF was detected than was injected. Finally, a PAF antagonist (WEB 2170) injected intraperitoneally prevented PAF-induced OME. This study demonstrates that PAF injected into the middle ear can induce OME and that PAF antagonists effectively prevent PAF-induced OME. These findings suggest that PAF plays an important role in the pathogenesis of OME.

Effect of inhibitors of leukotriene and/or platelet activating factor on killed H. influenzae induced experimental otitis media with effusion

“…All animals inoculated with formalin-killed H. influenzae in the control group developed MEE within 6 h of inoculation [11,15]. WEB-2170 has shown to prevent PAF induced OME effectively when it was administered intraperitoneally [11], and inhibited the PAF-induced mucous glycoprotein secretion [7,13]. SCH-37224 was developed as an anti-allergic agent that inhibits the formation of LTs and thromboxane release in vitro and in vivo [16,17].…”

“…Previously in our lab, metabolites of AA and PAF have been identified in human MEE as well as in experimentally induced middle ear effusions in animals [2,7,9,10]. LTs and PAF seem to be more pro-inflammatory than PGs, according to our previous animal studies [6,7,10]. LTC 4 , LTD 4 , and LTE 4 are called cystein LTs (CysLTs).…”

“…Inflammatory mediators multiply the level of inflammatory mediators by chemotactic activity. OME, metabolites of arachidonic acid (AA) and PAF seem to play an important role in the pathogenesis of OME [1,6,7]. Both AA metabolites and PAF are released by phospholipase A 2 from phospholipids.…”

The Presence of Platelet-Activating Factor-Acetylhydrolase in Human Middle Ear Effusions

“…Minami et al [6] reported that PAF, at concentrations over 10 -9 M, led to dysfunction of the eustachian tube, and Ganbo et al [5] found that PAF dose dependently inhibited mucociliary transport activity in the eustachian tube in vitro. In 1993, Rhee et al [2] reported that the injection of PAF into the middle ear of chinchillas with an intact eustachian tube induced COME and that PAF antagonists effectively prevented PAF-induced COME. Lin et al [3,4] reported that PAF induced excessive secretion of mucous glycoprotein in cultured chinchilla middle ear epithelial cells.…”

“…PAF is one of the most potent lipid mediators known and has a wide variety of physiological and pathophysiological actions [1]. PAF seems to play a major role in the production of middle ear effusion (MEE), as a result of increased vascular permeability [2], and stimulating epithelial secretory activity [3,4]. PAF also reduces the mucociliary activity on the middle ear [5] and causes eustachian tube dysfunction [6].…”