Interleukin-6, anxiety, and pre-treatment malnutrition in locally advanced head and neck cancer: a psychoneuroimmunological analysis.

BACKGROUND: Malnutrition and psychological distress are highly prevalent in patients with locally advanced head and neck cancer (LAHNC), although the biological mechanisms linking these conditions remain poorly understood. We investigated associations between systemic inflammation, gut-brain axis hormones, anxiety, and pre-treatment malnutrition within a psychoneuroimmunological framework. METHODS: A cross-sectional study was conducted in 74 patients with LAHNC prior to treatment initiation. Nutritional status was assessed using the Global Leadership Initiative on Malnutrition (GLIM) criteria, and anxiety using the Hospital Anxiety and Depression Scale (HADS-A). Circulating inflammatory cytokines and appetite-regulating hormones were quantified using multiplex immunoassays. Multivariable logistic regression and exploratory bootstrap mediation analyses were performed, together with an exploratory, bootstrap-based mediation analysis to evaluate whether anxiety represented a potential indirect pathway linking IL-6 and pre-treatment malnutrition. RESULTS: Pre-treatment malnutrition was identified in 40.5% of patients and clinically relevant anxiety in 36.5%. Elevated IL-6 and lower BMI were independently associated with malnutrition (OR 6.16, 95% CI 1.35-28.18; and OR 0.83, 95% CI 0.72-0.97, respectively). Elevated IL-6 was also independently associated with anxiety (OR 11.23, 95% CI 2.09-60.40). Elevated glucose-dependent insulinotropic polypeptide (GIP) levels were also associated with malnutrition after false discovery rate correction (q = 0.003). The exploratory mediation analysis suggested a non-significant trend toward partial mediation of the IL-6-malnutrition association through anxiety (the indirect effect did not reach statistical significance). Patients with malnutrition and anxiety exhibited significantly impaired health-related quality of life. CONCLUSION: These findings are consistent with a psychoneuroimmunological framework linking IL-6, anxiety, and pre-treatment malnutrition in LAHNC. Integrative strategies targeting inflammatory burden, nutritional status, and psychological distress may help improve clinical outcomes in this population.