leukotriene-c4 and Otitis-Media-with-Effusion

Leukotrienes B4, C4 (LTB4, LTC4) and prostaglandin E2 (PGE2) are arachidonic acid metabolites which are released from various types of cells, and are considered to be the mediators of inflammation because of their potent vascular permeability increasing activity (LTC4 and PGE2) and chemotactic activity (LTB4). In this study, to evaluate the involvement of arachidonic acid metabolites in otitis media with effusion, we measured the LTB4, LTC4 and PGE2 in rat middle ear effusion (MEE) by radioimmunoassay (RIA). SD rats weighing about 200g were used. The animals were divided into two groups, and lipopolysaccaride (LPS) or concanavalin A (ConA) was injected into the right middle ear cavity through the tympanic membrane. The left middle ear cavities were injected with 200 microliters of phosphate balanced buffered saline (PBS) and used as controls. After stimulation, middle ear effusion and accumulation of inflammatory cells such as neutrophils, macrophages, and lymphocytes was observed in the middle ear cavity. In contrast, no inflammatory cells were observed in the control ears. Proteins exudated into the middle ear cavity after LPS or ConA injection. The protein content increased up to 3 days, and then decreased. Substantial amounts of LTs and PG were detected in experimental rat OME, although hardly and LTs or PG was detected in the control ears or serum. LTs levels increased up to 7 days, and then decreased. PGE2 levels increased up to 3 days, and decreased thereafter. Dexamethasone effectively suppressed protein exudation, cell accumulation and production of arachidonic acid metabolites in the middle ear.

Topics: Animals; Dinoprostone; Leukotriene B4; Leukotriene C4; Male; Otitis Media with Effusion; Rats; Rats, Sprague-Dawley

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