ABSTRACT
In a rat model, we investigated the role of tumor necrosis factor (TNF) and interleukin-1 (IL-1) in endotoxin-induced middle ear effusions (MEEs). After the eustachian tube was obstructed, the middle ear was transtympanically injected with 35 microL of either 1) 1 mg/ mL lipopolysaccharide (LPS); 2) LPS and 100 micrograms TNF binding protein (TNFbp); 3) LPS and 1 microgram IL-1 receptor antagonist (IL-1ra); or 4) LPS, TNFbp, and IL-1ra. Every 2 hours, the fluid within the middle ear was collected, and the quantity of albumin in the fluid, an index of vascular leakage, was determined by enzyme-linked immunosorbent assay. After 6 hours, the middle ear was fixed for histologic analysis. The TNFbp significantly attenuated vascular extravasation into the middle ear. The IL-1ra did not significantly alter effusion development. These results indicate that TNF, but not IL-1, is a mediator of LPS-induced MEE. Therefore, TNFbp may represent a novel approach to the treatment of otitis media with effusion.
Subject(s)
Interleukin-1/physiology , Lipopolysaccharides , Otitis Media with Effusion/physiopathology , Pseudomonas aeruginosa , Receptors, Tumor Necrosis Factor , Tumor Necrosis Factor-alpha/physiology , Albumins/analysis , Animals , Carrier Proteins/pharmacology , Ear, Middle/pathology , Mucous Membrane/pathology , Otitis Media with Effusion/etiology , Otitis Media with Effusion/metabolism , Otitis Media with Effusion/pathology , Rats , Rats, Sprague-Dawley , Receptors, Interleukin-1/antagonists & inhibitors , Receptors, Tumor Necrosis Factor, Type I , Tumor Necrosis Factor Decoy ReceptorsABSTRACT
The presence of active nitric oxide synthase (NOS) in the spiral ganglion cells of the cochlea suggests that the neuromodulator nitric oxide (NO) may play a role in hearing. This study investigated the effects of sodium nitroprusside (SNP), an NO donor, upon cochlear function mediated through its activation of guanylate cyclase. In gerbils, cochlear compound action potential (CAP) thresholds were recorded after cochlear perfusions of control and test solutions in four experimental groups. Perfusions were performed using the following: artificial perilymph solution (APS); the NO donor SNP; the guanylate cyclase inhibitor methylene blue (MB); and sodium dodecyl sulfate (SDS), which facilitates MB entrance into cells. SNP caused significant elevations of CAP thresholds from baseline (25 dB SPL +/- 1.54 dB to 64.3 dB SPL +/- 2.54 dB). SNP with MB also resulted in significant CAP threshold elevations (29.4 dB SPL +/- 4.27 dB to 38.1 dB SPL +/- 4.0 dB); however, these elevations were significantly lower than those seen in SNP perfusions without MB. Drilling perfusion holes and perfusion of APS, APS/SDS, and MB/SDS/APS solutions did not significantly affect CAP thresholds. These results suggest that the NO donor nitroprusside does affect cochlear neuromodulation and effects this mediation in part through NO activation of guanylate cyclase.
