Inflammatory Signatures of Tinnitus in Patients and Mice

Tinnitus is a common refractory disorder with complex mechanisms. Emerging evidence suggests that inflammation plays key roles in tinnitus pathogenesis; however, its overall inflammatory signatures remain underinvestigated. This study integrates transcriptomic data from patients with tinnitus and a noise-induced mouse model to identify conserved neuroinflammatory pathways. RNA sequencing of blood samples from patients with tinnitus and concurrent hearing loss revealed significant enrichment of immune-related pathways. Similar inflammatory signatures were detected through transcriptomic and cytokine profiling of the peripheral blood samples obtained from mice with noise-induced hearing loss. Microglial activation and elevated pro-inflammatory cytokines were observed in the cochlear nucleus and auditory cortex during the onset of noise-induced tinnitus. Pharmacological inhibition of microglial activation or tumor necrosis factor-α signaling alleviated tinnitus-like behaviors in mice. These findings reveal a dynamic peripheral-to-central inflammatory axis in tinnitus as well as identify blood-based biomarkers and auditory-center inflammation as potential therapeutic targets.