Role of tumor necrosis factor-alpha in sensorineural hearing loss after bacterial meningitis.
OBJECTIVE
Blockade of tumor necrosis factor-alpha with tumor necrosis factor-alpha antibody will reduce the extent of cochlear injury and hearing loss associated with Streptococcus pneumoniae meningitis.


BACKGROUND
Inflammatory mediators play a significant role in the morbidity associated with bacterial meningitis, including hearing loss and labyrinthitis ossificans. Previous studies have shown the attenuation of hearing loss by the nonspecific blockade of such pathways.


METHODS
Fifty Mongolian gerbils were divided into four groups. Auditory brainstem response testing was conducted to measure hearing thresholds. Streptococcus pneumoniae meningitis was induced in Groups 1 and 2. Group 2 was then given a single intraperitoneal injection of tumor necrosis factor-alpha antibody, whereas Group 1 received phosphate-buffered saline. Uninfected animals in Groups 3 and 4 were implanted with osmotic pumps that delivered a continuous 8-day intrathecal flow of either tumor necrosis factor-alpha (Group 4) or phosphate-buffered saline (Group 3). After 6 weeks, auditory brainstem response testing was repeated. The cochleas were harvested and analyzed histomorphometrically.


RESULTS
Group 2 animals with Streptococcus pneumoniae meningitis that also received tumor necrosis factor-alpha antibody developed significantly less hearing loss than Group 1 animals with meningitis alone. The decrease in the average threshold at 4, 8, 16, and 32 kHz was 31, 30, 25, and 28 dB sound pressure level, respectively (p < 0.0092 for each). Furthermore, histomorphometric analysis showed significantly less damage to the organ of Corti, spiral ganglion, spiral ligament, and stria vascularis in Group 2. Conversely, tumor necrosis factor-alpha induced meningitis animals (Group 3) showed increased hearing loss compared with phosphate-buffered saline controls (Group 4), with p < 0.0001 at all frequencies.


CONCLUSIONS
Tumor necrosis factor-alpha plays an important role in cochlear injury after bacterial meningitis. Blockade of tumor necrosis factor-alpha reduces postmeningitic hearing loss and cochlear injury. Induction of meningitis with intrathecal tumor necrosis factor-alpha also resulted in hearing loss and cochlear injury similar to bacterial meningitis.
Aminpour
Shervin
S
Department of Otolaryngology Head and Neck Surgery, University of California, Davis, School of Medicine, Davis, California 95616, USA.
Tinling
Steven P
SP
Brodie
Hilary A
HA
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001299:Audiometry; D001309:Auditory Threshold; D003051:Cochlea / Q000187:drug effects / Q000473:pathology; D016057:Evoked Potentials, Auditory, Brain Stem; D005849:Gerbillinae; D006319:Hearing Loss, Sensorineural / Q000209:etiology* / Q000503:physiopathology; D007260:Infusion Pumps; D008581:Meningitis / Q000139:chemically induced / Q000150:complications; D008586:Meningitis, Pneumococcal / Q000150:complications* / Q000401:mortality / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha