Immunoinflammatory mechanisms and targeted therapy of sudden deafness

LI Ge; ZHANG Wenjing; ZHANG Yubo

doi:10.3969/j.issn.1672-2922.2026.03.007

Abstract：Sudden sensorineural hearing loss(SSNHL)refers to idiopathic sensorineural hearing loss occurring within 72 hours,characterized by a hearing loss of at least 30 dB at two adjacent frequencies.The annual incidence of this condition has shown an increasing trend in recent years,primarily affecting the middle-aged population.Currently,systemic corticosteroid therapy is the first-line treatment for SSNHL.However,approximately 30%to 50%of patients exhibit poor response to treatment,and some experience significant side effects from corticosteroid use,making developing new therapeutic approaches crucial.Systemic immune dysregulation affects the local microenvironment in the inner ear through inflammatory factors,autoantibodies and immune cell infiltration,disrupting its immune-privileged state and ultimately leading to unilateral hearing loss.Abnormal immune responses,such as autoantibody deposition,T-cell subset dysregulation,and macrophage hyperactivation,further exacerbate inner ear tissue damage.Additionally,biomarkers such as NLR and PLR in peripheral blood,as well as HSP70 and prestin in the inner ear,are associated with disease progression.Clinically,targeted therapies based on immunoinflammatory mechanisms have achieved notable progress,including those targeting the NLRP3 pathway,JNK signaling pathway and antioxidant stress.Furthermore,emerging research on cell-protective and functional-repairing small-molecule drugs and gene therapy provides a foundation for treating sudden deafness.However,current research still faces multiple challenges,such as limited efficacy of existing treatments,significant heterogeneity in biomarker profiles,drug delivery barriers due to the blood-labyrinth barrier,and high heterogeneity in etiology.Future research needs to achieve breakthroughs in key areas such as in-depth elucidation of pathogenesis,precise biomarker screening and development of efficient drug delivery systems,thereby promoting a systematic improvement in the clinical diagnosis and treatment of SSNHL.