Hypothesis Blockade of tumor necrosis factor α (TNF-α) with TNF-α antibody will reduce the extent of intracochlear fibrosis, ossification, 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 non-specific blockade of such pathways.
Methods Fifty Mongolian gerbils were divided into 4 groups. Auditory brainstem response testing (ABR) 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 TNF-α antibody while group 1 received normal saline. Uninfected animals in groups 3 and 4 were implanted with osmotic pumps that delivered a continuous 8 day intrathecal flow of either TNF-α or phosphate buffered saline (PBS). After 6 weeks, ABR testing was repeated.
Results Group 2 animals with S. pneumoniae meningitis which also received TNF-α 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 SPL 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, TNF-α induced meningitis animals (group3) showed increased hearing loss compared to PBS controls (group4) with P ≤ 0.0001 at all frequencies.
Conclusions TNF-α plays an important role in cochlear injury following bacterial meningitis. Blockade of TNF-α reduces post-meningitic hearing loss and cochlear injury. Induction of meningitis with intrathecal also resulted in hearing loss and cochlear injury similar to bacterial meningitis.
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