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Background <p>Radiation-induced oral mucositis requires predictive biomarkers for personalized therapy. We evaluated salivary IL-6 for predicting severe mucositis and response to food-grade bee products.</p> Methods <p>Secondary analysis of 51 head/neck cancer patients randomized to honey (<i>n</i> = 15), Taiwanese green propolis (TGP, <i>n</i> = 17), or usual-care (<i>n</i> = 19). Both interventions used standardized preparations (10&#xa0;g in 20&#xa0;mL water, 10&#xa0;mL TID). Salivary cytokines were analyzed using ELISA at baseline and during early radiotherapy.</p> Results <p>Salivary IL-6 at week 3 of radiotherapy demonstrated superior predictive performance (AUC = 0.780, 95% CI: 0.610–0.950, <i>p</i> = 0.026) compared to other cytokines, with an optimal cutoff of 286.25&#xa0;pg/mL (sensitivity 72%, specificity 81%, Cohen's d = 0.92). Patients with elevated IL-6 (≥ 286.25&#xa0;pg/mL) showed enhanced response to interventions, with numbers needed to treat of 2.3 for honey and 2.6 for TGP versus 6.7 and 5.9 in low-risk patients. Longitudinal analysis revealed distinct anti-inflammatory patterns: honey suppressed IL-1β at week 3 (<i>p</i> = 0.022), while TGP affected TNF-α at week 2 (<i>p</i> = 0.047). Post-hoc power analysis indicated 70% power for the primary analysis, suggesting these findings represent preliminary evidence requiring validation.</p> Conclusion <p>Salivary IL-6 provides promising preliminary evidence for risk stratification in radiation-induced OM. The 286.25&#xa0;pg/mL threshold may guide selection of food-grade complementary therapies, with both honey and TGP showing enhanced efficacy in high-risk patients. While limited by moderate statistical power (70%), these findings support the potential for biomarker-guided personalized supportive care using accessible, food-grade interventions. Prospective validation in larger cohorts (<i>N</i> ≥ 100) is warranted to confirm the clinical utility of IL-6-guided therapy selection.</p> Graphical Abstract <p></p>

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Baseline salivary IL-6 as a predictive biomarker for complementary therapy response in radiation-induced oral mucositis

  • 期刊论文

  • 发表日期：

    2026年4月23日

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  • Hsu-Chieh Chang,
  • Yue-Wen Chen,
  • Wen-Yen Huang,
  • Jo-Ting Tsai,
  • Chia-Yu Wu,
  • Made Satya Nugraha Gautama,
  • Tsai-Wei Huang

摘要

Background

Radiation-induced oral mucositis requires predictive biomarkers for personalized therapy. We evaluated salivary IL-6 for predicting severe mucositis and response to food-grade bee products.

Methods

Secondary analysis of 51 head/neck cancer patients randomized to honey (n = 15), Taiwanese green propolis (TGP, n = 17), or usual-care (n = 19). Both interventions used standardized preparations (10 g in 20 mL water, 10 mL TID). Salivary cytokines were analyzed using ELISA at baseline and during early radiotherapy.

Results

Salivary IL-6 at week 3 of radiotherapy demonstrated superior predictive performance (AUC = 0.780, 95% CI: 0.610–0.950, p = 0.026) compared to other cytokines, with an optimal cutoff of 286.25 pg/mL (sensitivity 72%, specificity 81%, Cohen's d = 0.92). Patients with elevated IL-6 (≥ 286.25 pg/mL) showed enhanced response to interventions, with numbers needed to treat of 2.3 for honey and 2.6 for TGP versus 6.7 and 5.9 in low-risk patients. Longitudinal analysis revealed distinct anti-inflammatory patterns: honey suppressed IL-1β at week 3 (p = 0.022), while TGP affected TNF-α at week 2 (p = 0.047). Post-hoc power analysis indicated 70% power for the primary analysis, suggesting these findings represent preliminary evidence requiring validation.

Conclusion

Salivary IL-6 provides promising preliminary evidence for risk stratification in radiation-induced OM. The 286.25 pg/mL threshold may guide selection of food-grade complementary therapies, with both honey and TGP showing enhanced efficacy in high-risk patients. While limited by moderate statistical power (70%), these findings support the potential for biomarker-guided personalized supportive care using accessible, food-grade interventions. Prospective validation in larger cohorts (N ≥ 100) is warranted to confirm the clinical utility of IL-6-guided therapy selection.

Graphical Abstract