Plasma Inflammatory Biomarkers and Risk of Incident Tinnitus: A Longitudinal Study

OBJECTIVES: Tinnitus is a common and debilitating condition characterized by phantom auditory perception with no external source of sound. The role of inflammation in tinnitus etiology has been investigated, but findings are inconsistent, with no longitudinal human studies. We investigated the independent associations of three plasma biomarkers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], tumor necrosis factor receptor 2 [TNFR-2]) and risk of incident frequent and daily tinnitus. METHODS: This prospective cohort study followed 4149 women (ages 31 to 48) in the Nurses' Health Study II from 1995 to 2021. Biomarkers were ascertained from previous nested case-control studies, and tinnitus was ascertained from biennial questionnaires. Multivariable-adjusted Cox proportional hazards regression was used to evaluate independent associations between inflammatory biomarkers and risk of incident frequent tinnitus (occurring several days per week or more) and daily tinnitus. RESULTS: There were no significant associations between plasma levels of CRP, IL-6, or TNFR-2 biomarkers and increased risk of incident tinnitus, both before and after adjustment for potential confounders. For the primary outcome of frequent tinnitus, the highest category of each biomarker yielded multivariable-adjusted hazard ratios (95% confidence interval) of 0.78 (0.54 to 1.13) for CRP; 0.69 (0.46 to 1.04) for IL-6; and 1.06 (0.77 to 1.44) for TNFR-2. For daily tinnitus, multivariable-adjusted hazard ratios were 0.72 (0.47 to 1.09) for CRP; 0.67 (0.42 to 1.07) for IL-6; and 0.91 (0.63 to 1.29) for TNFR-2. Tests for linear trend across biomarker levels were nonsignificant. CONCLUSION: Three plasma biomarkers of inflammation-CRP, IL-6, and TNFR-2-were not significantly associated with increased risk of incident tinnitus in women. Our data suggest that markers of systemic inflammation may not be indicators of vulnerability to tinnitus.