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Life sciences · Journal article
Frontiers in Oral Health · October 14, 2026
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Background Radiotherapy for head and neck cancer (HNC) frequently causes irreversible damage to salivary glands, which severely impairs quality of life and is difficult to treat. Preclinical studies indicated that macrophages and related inflammatory processes are essential for the pathogenesis and treatment of this adverse effect. The study on changes of salivary cytokines after radiotherapy in HNC patients is necessary to validate the translational potential of these preclinical findings. Methods 16 patients with newly diagnosed HNC were enrolled for collecting whole saliva before and one and three months after radiotherapy. Saliva was analyzed using a magnetic luminex assay to quantify 25 cytokines. Changes of salivary cytokine levels and secretion rates between time points were evaluated using paired t-tests. Results Chewing-stimulated saliva flow rates significantly decreased one and three months after radiotherapy. Salivary levels of 10 pro-inflammatory cytokines significantly increased at one month and three months, respectively, with 8 of them increased at both timepoints. In terms of the flow rate-adjusted saliva cytokine levels (secretion rates), only CCL2 and GDF15 significantly increased at both time points, whereas 5 other cytokines increased either one month or three months. In mouse salivary glands after radiation, most of these cytokines also significantly increased, which was reversed by a therapy effectively preserved saliva secretion after radiation. Conclusion Radiotherapy in HNC patients increased salivary levels and rates of multiple pro-inflammatory cytokines, which encourages further studies of these salivary cytokines as markers for the prognosis and personalized treatment of dry mouth after radiotherapy. Clinical relevance The persistent increases of salivary concentrations of many pro-inflammatory cytokines after radiotherapy may exacerbate oral health issues together with the decrease of saliva secretion. The increases in salivary rates of multiple pro-inflammatory cytokines suggest prolonged inflammation and stress in salivary glands, which contributes to long-term dry mouth and are promising therapeutic targets.