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-α (tnf-α) and/or interleukin-1β (il-1β) during tinnitus have not been previously reported. we evaluated tinnitus and mrna expression levels of tnf-α,il-1β,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-α,il-1β,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-α 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-1β 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-α,il-1β,and nr2b genes in cochlea and ic. in addition,expression levels of the tnf-α gene were positively correlated with those of the nr2bgene in both cochlea and ic; whereas,the expression levels of the il-1β 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-α and il-1β 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. © 2011 hwang et al; licensee biomed central ltd.