Jiang Lijie, Zhou Min, Deng Jie, Sun Yueqi, Zuo Kejun, Zheng Rui, Shi Jianbo, Lai Yinyan
The Otorhinolaryngology Hospital, First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, No. 58 Zhongshan Er Road, Guangzhou, People's Republic of China.
Eur Arch Otorhinolaryngol. 2019 Jan;276(1):131-137. doi: 10.1007/s00405-018-5201-3. Epub 2018 Nov 16.
Glucocorticoids are the first-line medical treatment for chronic rhinosinusitis with nasal polyps (CRSwNP), whose local metabolism is catalyzed by 11β-HSD1 and 11β-HSD2. This study investigates the role of 11β-HSD1 and 11β-HSD2 on the glucocorticoid response of CRSwNP patients and the pathogenic mechanism of these polyps.
Forty-three adult CRSwNP patients were enrolled in this study. We evaluated the endoscopic scores by a nasal polyp grading system before and after treatment. We estimated the response to glucocorticoids by the total endoscopic scores. The logistic regression models and inflammatory characteristic curves were conducted to explore the prediction of the response to glucocorticoid in CRSwNP. The expression of 11β-HSD1 and 11β-HSD2 on human sinonasal epithelial cells (HSECS) was measured under the stimulation of toll-like receptor agonists and dexamethasone.
The endoscopic scores in the CRSwNP group declined, the expression of 11β-HSD1/11β-HSD2 increased (r = 0.5276, P = 0.0011), and the cutoff value of the ratio of 11β-HSD1/11β-HSD2 was 0.4654 (sensitivity 79.17%, specificity 88.89%). Dexamethasone induced a decrease in the ratio of 11β-HSD1/11β-HSD2 (P = 0.049) by the stimulation of PGN-BS.
We found a strong correlation between the response to glucocorticoids and the ratio of 11β-HSD1/11β-HSD2, which could be used as a marker in predicting the level of tissue response to glucocorticoid therapy in CRSwNP. In addition, PGN-BS could also be a therapeutic target, as it is the negative factor that will decrease the sensitivity of glucocorticoids by reducing the ratio of 11β-HSD1/11β-HSD2.
糖皮质激素是慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）的一线药物治疗，其局部代谢由11β-羟基类固醇脱氢酶1（11β-HSD1）和11β-羟基类固醇脱氢酶2（11β-HSD2）催化。本研究调查11β-HSD1和11β-HSD2在CRSwNP患者糖皮质激素反应中的作用以及这些息肉的致病机制。
43例成年CRSwNP患者纳入本研究。我们通过鼻息肉分级系统在治疗前后评估内镜评分。我们通过总内镜评分评估对糖皮质激素的反应。采用逻辑回归模型和炎症特征曲线探讨CRSwNP中对糖皮质激素反应的预测。在 toll 样受体激动剂和地塞米松刺激下，检测人鼻窦上皮细胞（HSECS）上11β-HSD1和11β-HSD2的表达。
CRSwNP组内镜评分下降，11β-HSD1/11β-HSD2表达增加（r = 0.5276，P = 0.0011），11β-HSD1/11β-HSD2比值的截断值为0.4654（敏感性79.17%，特异性88.89%）。地塞米松通过PGN-BS刺激导致11β-HSD1/11β-HSD2比值降低（P = 0.049）。
我们发现糖皮质激素反应与11β-HSD1/11β-HSD2比值之间存在强相关性，这可作为预测CRSwNP中组织对糖皮质激素治疗反应水平的标志物。此外，PGN-BS也可能是一个治疗靶点，因为它是通过降低11β-HSD1/11β-HSD2比值来降低糖皮质激素敏感性的负性因子。
