Expression of tumor necrosis factor-α and interleukin-1β genes in the cochlea and inferior colliculus in salicylate-induced tinnitus

Background: Changes in the gene expressions for tumor necrosis factor-alpha (TNF-alpha) and/or interleukin-1 beta (IL-1 beta) during tinnitus have not been previously reported. We evaluated tinnitus and mRNA expression levels of TNF-alpha, IL-1 beta, and N-methyl D-aspartate receptor subunit 2B (NR2B) genes in cochlea and inferior colliculus (IC) of mice after intraperitoneal injections of salicylate. Methods: Forty-eight 3-month-old male SAMP8 mice were randomly and equally divided into two groups: salicylate-treated and saline-treated. All mice were trained to perform an active avoidance task for 5 days. Once conditioned, an active avoidance task was performed 2 hours after daily intraperitoneal injections of saline, either alone or containing 300 mg/kg sodium salicylate. Total numbers of times (tinnitus score) the mice climbed during the inter-trial silent period for 10 trials were recorded daily for 4 days (days 7 to 10), and then mice were euthanized for determination of mRNA expression levels of TNF-alpha, IL-1 beta, and NR2B genes in cochlea and IC at day 10. Results: Tinnitus scores increased in response to daily salicylate treatments. The mRNA expression levels of TNF-alpha increased significantly for the salicylate-treated group compared to the control group in both cochlea (1.89 +/- 0.22 vs. 0.87 +/- 0.07, P < 0.0001) and IC (2.12 +/- 0.23 vs. 1.73 +/- 0.22, p = 0.0040). mRNA expression levels for the IL-1 beta gene also increased significantly in the salicylate group compared to the control group in both cochlea (3.50 +/- 1.05 vs. 2.80 +/- 0.28, p < 0.0001) and IC (2.94 +/- 0.51 versus 1.24 +/- 0.52, p = 0.0013). Linear regression analysis revealed a significant positive association between tinnitus scores and expression levels of TNF-alpha, IL-1 beta, and NR2B genes in cochlea and IC. In addition, expression levels of the TNF-alpha gene were positively correlated with those of the NR2Bgene in both cochlea and IC; whereas, the expression levels of the IL-1 beta gene was positively correlated with that of the NR2B gene in IC, but not in cochlea. Conclusion: We conclude that salicylate treatment resulting in tinnitus augments expression of the TNF-alpha and IL-1 beta genes in cochlea and IC of mice, and we suggest that these proinflammatory cytokines might lead to tinnitus directly or via modulating the NMDA receptor.