leukotriene-d4 and Otitis-Media-with-Effusion

inflammatory mediators such as prostaglandins (PGs), leukotrienes (LTs), and platelet-activating factor (PAF) have been identified in human middle ear effusions (MEEs), as well as in the experimentally induced MEEs of animals. However, the exact function of LTs in the middle ear cavity is still unknown. In this study, the role of LTs was investigated using an experimental model in which OME was induced by LTD4.. to examine whether leukotrienes (LTs) induce otitis media with effusion (OME), 2x10(-6), 2x10(-5), 1x10(-4) and 2x10(-4) M of LTD4 was injected into the rat ear. The severity of OME was assessed based on the histological findings. The concentrations of IL1-beta, TNF-alpha, and GRO/CINC-1 in MEE were also measured. Additionally the therapeutic efficacy of a specific LTs antagonist, pranlukast on experimental OME was investigated.. all ears developed middle ear effusion (MEE) within 24 h and about 50% of the animals continued to demonstrate MEE for 14 days in the 1x10(-4) and 2x10(-4) M groups. The cytokine levels seemed to correspond well with the persistence of OME. The oral administration of a specific LTs antagonist, pranlukast, was found to alleviate the experimental OME.. these findings suggest that LTs appear to plays an important role in the pathogenesis of OME.

Topics: Animals; Chromones; Cytokines; Humans; Leukotriene Antagonists; Leukotriene D4; Male; Models, Animal; Otitis Media with Effusion; Rats; Rats, Wistar; Severity of Illness Index

The therapeutic effect of oxatomide on experimental otitis media with effusion (OME) induced by secondary immune response was investigated in chinchillas. Oxatomide was administered daily in three different doses (5, 10, 30 mg/kg b.w.t.) for a period of 2 weeks, starting 2 days after the instillation of keyhole limpet hemocyanin (KLH) into the tympanic cavity. The severity of OME was assessed by observing the eardrum under a surgical microscope, by tympanography, and by histological findings. The concentrations of leukotriene C4 and LTD4 in middle ear effusion (MEE) were also measured, 7 days after the KLH instillation. It was found that oral administration of oxatomide in dosages of 10 and 30 mg/kg alleviated the experimental OME. The mean LTD4 concentration measured in MEE from chinchillas given 30 mg oxatomide was significantly lower than that measured in the control group. The radioactivity of 14C-labelled oxatomide in MEE and the autoradiographic findings revealed that orally administered oxatomide was rapidly absorbed from the digestive tract and transported to the middle ear via blood circulation. The findings suggest that the effect of oxatomide can be anticipated in patients with OME.

Topics: Acoustic Impedance Tests; Animals; Autoradiography; Chinchilla; Ear, Middle; Eustachian Tube; Leukotriene D4; Otitis Media with Effusion; Piperazines; Tympanic Membrane

The effect of leukotrienes C4 (LTC4) and D4 (LTD4) and prostaglandin E2 (PGE2) on mucociliary clearance of the eustachian tube was investigated in vitro and in vivo. Normal ciliated epithelium was obtained from the eustachian tube of guinea pigs and incubated separately with LTC4, LTD4, and PGE2 at concentrations of 10(-8) mol/L and 10(-6) mol/L. Ciliary activity was measured photoelectrically. Leukotriene D4 progressively inhibited ciliary activity, while PGE2 promoted it. Leukotriene C4 also induced ciliary inhibition. One milliliter each of 10(-5) mol/L LTC4, LTD4, and PGE2 was directly injected into the tympanic bullae of chinchillas under anesthesia. The middle ears were examined by otomicroscopy, tympanometry, and auditory brain stem response over time. Clearance of middle ear effusion was delayed by LTC4 and LTD4, as compared with PGE2 and the control. These findings indicate that LTC4 and LTD4 inhibit mucociliary clearance of the eustachian tube.

Topics: Animals; Chinchilla; Dinoprostone; Eustachian Tube; Guinea Pigs; In Vitro Techniques; Leukotriene C4; Leukotriene D4; Male; Mucociliary Clearance; Otitis Media with Effusion