Department of Physics, University of Oslo, 0371 Oslo, Norway.
Institute of Oral Biology, University of Oslo, 0372 Oslo, Norway.
Int J Mol Sci. 2023 Oct 16;24(20):15218. doi: 10.3390/ijms242015218.
Cytokines are mediators of inflammation that could lead to fibrosis. The aim was to monitor cytokine levels in saliva and serum after locally fractionated radiotherapy of the head and neck in mice and investigate associations with salivary gland fibrosis and hyposalivation. C57BL/6 mice were randomized to sham or X-ray irradiation of 66 Gy in 10 fractions over 5 days. Blood and saliva were collected on days -7, 5, 35, 80, and 105 following cytokine analysis. The harvested submandibular salivary gland was assessed for the presence of fibrosis. Decision tree regression analysis was used to investigate whether cytokine levels could predict late endpoints in terms of hyposalivation or fibrosis. Significant formation of fibrosis in gland tissue and reduced saliva production was found after irradiation. The pro-inflammatory cytokines IL-1α, TNF, TIMP1, G-CSF, KC, and MIP-1α showed increased levels in saliva in irradiated mice and a strong correlation with late endpoints. The decision tree analysis largely separated controls from irradiated animals, with IL-1α being the strongest predictor. Pro-inflammatory cytokines in saliva, but not in serum, were associated with late endpoints. This indicates that cytokine expression in saliva is a good biomarker for local salivary gland damage with IL-1α as the strongest single predictor.
细胞因子是炎症的介质，可能导致纤维化。目的是监测小鼠头颈部局部分次放射治疗后唾液和血清中的细胞因子水平，并研究其与唾液腺纤维化和唾液分泌减少的关系。将 C57BL/6 小鼠随机分为假照射或 X 射线照射 66Gy，分 10 次，每天一次，共 5 天。在收集细胞因子分析样本后，在第-7、5、35、80 和 105 天采集血液和唾液。评估颌下腺中是否存在纤维化。决策树回归分析用于研究细胞因子水平是否可以预测唾液分泌减少或纤维化等晚期终点。照射后发现腺体组织中明显形成纤维化和唾液分泌减少。在接受照射的小鼠的唾液中，促炎细胞因子 IL-1α、TNF、TIMP1、G-CSF、KC 和 MIP-1α 水平升高，并与晚期终点密切相关。决策树分析在很大程度上将对照组与照射组分开，IL-1α 是最强的预测因子。唾液中的促炎细胞因子与晚期终点相关，但血清中无相关性。这表明唾液中的细胞因子表达是局部唾液腺损伤的良好生物标志物，其中 IL-1α 是最强的单一预测因子。
