Roles of IFN-γ, IL-17, and Peripheral Blood Neutrophils in Olfactory Dysfunction in Non-Eosinophilic CRSwNP

BackgroundOlfactory dysfunction (OD) is a significant symptom in non-eosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP), but its non-type 2 inflammation-driven mechanisms remain unclear.ObjectiveTo investigate the roles of local nasal non-type 2 inflammatory cytokines and systemic immune indicators in neCRSwNP-associated OD.MethodsSeventy-nine neCRSwNP patients were enrolled and divided into neCRSwNP with OD (neCRSwNP-wOD, n = 49) and neCRSwNP without OD (neCRSwNP-woOD, n = 30) groups. Olfactory function was assessed using the T&T Olfactometer. Nasal mucus cytokines (IFN-γ, TNF-α, IL-1β, IL-17) were measured by ELISA. Peripheral blood inflammatory indicators including absolute neutrophil count (Neut), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), were analyzed. Statistical methods included the Mann-Whitney U test, Spearman correlation analysis, multivariate logistic regression, and ROC curve analysis.ResultsNasal IFN-γ and IL-17 levels were significantly elevated in the OD group (both P < 0.05), while TNF-α and IL-1β showed no difference. Patients with OD also exhibited higher Neut, NLR, and SII (all P < 0.05). Olfactory scores strongly correlated with Neut (r = 0.639, P < 0.01) and moderately with IFN-γ (r = 0.533, P < 0.01). Multivariate regression identified IFN-γ, IL-17, and Neut as independent risk factors for OD. ROC analysis indicated that Neut had the highest predictive accuracy (AUC = 0.839), and a combined model of three indicators (Lund-Kennedy score, IL-17 and Neut) achieved excellent diagnostic performance (AUC = 0.964).ConclusionOlfactory dysfunction in neCRSwNP is associated with the combined involvement of local Th1/Th17 pathway activation (IFN-γ/IL-17) and neutrophil-mediated systemic inflammation. IFN-γ, IL-17, and peripheral blood neutrophils may be involved in the development of olfactory dysfunction in neCRSwNP.