Korean J Otolaryngol-Head Neck Surg.  2001 Aug;44(8):794-799.

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

• Rhee CK
• Jeon SJ
• Jung SW
• Lee CH
• Oh CH

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.

Keyword

Bacterial meningitis; TNF-alpha; IL-1beta; L-NAME; NO

MeSH Terms

Animals
Cisterna Magna
Cytokines
Evoked Potentials, Auditory, Brain Stem
Guinea Pigs*
Guinea*
Hair
Hearing Loss*
Hearing Loss, Sensorineural
Hearing*
Humans
Meningitis, Bacterial
Microscopy, Electron, Scanning
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Tumor Necrosis Factor-alpha*
Cytokines
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Tumor Necrosis Factor-alpha