The protective effect of nitirc oxide synthase inhibitor on hearing loss induced by TNF-alpha and IL-1beta injection into CSF in guinea pigs / 대한이비인후과학회지

ABSTRACT

BACKGROUND AND OBJECTIVES: One of the most serious complications of bacterial meningitis, particularly in childhood, is sensorineural hearing loss; yet the mechanisms of this hearing loss are not clearly understood. It is also known that the levels of TNF-alpha, IL-1beta in CSF are significantly elevated in bacterial meningitis patients. This study is designed to evaluate the role of nitric oxide (NO) in the ototoxic effect of TNF-alpha and IL-1beta injected into CSF of guinea pigs. MATERIALS AND METHODS: Twenty-six guinea pigs (52 ears) were randomly assigned into six groups consisting of a control group, a NG-nitro-L-arginine methyl ester (L-NAME) group, a TNF-alpha group, a TNF-alpha plus L-NAME group, a IL-1beta group and a IL-1beta plus L-NAME group. The thresh shifts of the auditory brain stem response (ABR) were measured before, 6 and 24 hours after the administration of cytokines. TNF-alpha and IL-1beta were directly injected into the cisterna magna in a dosage of 0.1 microgram in 10 microgram/ microliter concentration. L-NAME, a NO synthase (NOS) inhibitor, was injected intraperitoneally 30 minutes prior to the administration of cytokines. Scanning electron microscopy was used to find the morphological damage of the hair cells. RESULTS: In TNF-alpha group, the ABR thresh shift after injection of 6 and 24 hours was 19.2 +/- 10.2 dB, 18.3 +/- 10.3 dB, in the TNF-alpha plus L-NAME group, 3.3 +/- 2.6 dB, 8.3 +/- 4.1 dB, in the IL-1beta group, 6.9 +/- 4.6 dB, 11.25 +/- 8.3 dB, and in the IL-1beta plus L-NAME group, 1.7 +/- 2.7 dB, 1.3 +/- 2.5 dB, respectively. There was damage in the 2nd, 3rd row of the outer hair cells in the TNF-alpha and IL-1beta group. CONCLUSION: This study suggests that the sensorineural hearing loss associated with bacterial meningitis is caused in part by the actions of proinflammatory cytokines such as TNF-alpha, IL-1beta and that these are mediated by NO.