This review deals with the characteristics of various inflammatory mediators identified in the middle ear during otitis media and in cholesteatoma. The role of each inflammatory mediator in the pathogenesis of otitis media and cholesteatoma has been discussed. Further, the relation of each inflammatory mediator to the pathophysiology of the middle and inner ear along with its mechanisms of pathological change has been described. The mechanisms of hearing loss including sensorineural hearing loss (SNHL) as a sequela of otitis media are also discussed. The passage of inflammatory mediators through the round window membrane into the scala tympani is indicated. In an experimental animal model, an application of cytokines and lipopolysaccharide (LPS), a bacterial toxin, on the round window membrane induced sensorineural hearing loss as identified through auditory brainstem response threshold shifts. An increase in permeability of the blood-labyrinth barrier (BLB) was observed following application of these inflammatory mediators and LPS. The leakage of the blood components into the lateral wall of the cochlea through an increase in BLB permeability appears to be related to the sensorineural hearing loss by hindering K+ recycling through the lateral wall disrupting the ion homeostasis of the endolymph. Further studies on the roles of various inflammatory mediators and bacterial toxins in inducing the sensorineumral hearing loss in otitis media should be pursued.

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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.

It has already been demonstrated in human and animal systems that PGE2 is a suppressor signal for many immune functions. These include T-lymphocyte blastogenesis, natural killer cell activity, and cytolytic T-lymphocyte activity. These functions are important for destruction of tumor cells. Conceivably, suppression of these functions by excessive PGE2 restricts tumor cell kill, and reversal of suppression by an inhibitor of prostaglandin synthesis such as indomethacin could increase tumor cell kill. The purpose of this study was to determine the kind of prostaglandins (PGs) produced by tissues with squamous cell carcinoma of head and neck and to measure the concentrations of PGE2, 6-keto-PGF1 alpha, and thromboxane (Tx) B2 in the tumor tissue and in the corresponding control tissue. Tumor and normal control tissues at the margin of the resection were obtained from surgical specimens. The production of PGs was determined by incubation of tissue homogenates with 14C-arachidonic acid, by thin layer chromatography, autoradiography, and scintillation counting. Concentrations of PGs were measured by radioimmunoassay. Tumor tissues produced PGD2, E2, TxB2, F2 alpha, and 6-keto-F1 alpha, and 15-, 12-, and 5-monohydroxyeicosatetraenoic acid (HETE). Concentrations of PGE2 were four times higher in the tumor tissues compared to those in control tissues. There was no difference between the levels of TxB2 and 6-keto-PGF1 alpha in the tumor tissues and those in control tissues. The results of this study will serve as basic information necessary for the potential use of inhibitors of PG-synthesis in the treatment of head and neck carcinoma.