Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, United States.
Monell Chemical Senses Center, Philadelphia, PA, United States.
Front Immunol. 2018 Mar 28;9:624. doi: 10.3389/fimmu.2018.00624. eCollection 2018.
Bitter (T2R) and sweet (T1R) taste receptors in the airway are important in innate immune defense, and variations in taste receptor functionality in one T2R (T2R38) correlate with disease status and disease severity in chronic rhinosinusitis (CRS). Quinine is a bitter compound that is an agonist for several T2Rs also expressed on sinonasal cells, but not for T2R38. Because of this property, quinine may stimulate innate immune defense mechanisms in the airway, and functional differences in quinine perception may be reflective of disease status in CRS.
Demographic and taste intensity data were collected prospectively from CRS patients and non-CRS control subjects. Sinonasal tissue from patients undergoing rhinologic surgery was also collected and grown at an air-liquid interface (ALI). Nitric oxide (NO) production and dynamic regulation of ciliary beat frequency in response to quinine stimulation were assessed .
Quinine reliably increased ciliary beat frequency and NO production in ALI cultures in a manner consistent with T2R activation ( < 0.01). Quinine taste intensity rating was performed in 328 CRS patients and 287 control subjects demonstrating that CRS with nasal polyps (CRSwNP) patients rated quinine as significantly less intense than did control subjects.
Quinine stimulates airway innate immune defenses by increasing ciliary beat frequency and stimulating NO production in a manner fitting with T2R activation. Patient variability in quinine sensitivity is observed in taste intensity ratings, and gustatory quinine "insensitivity" is associated with CRSwNP status. Thus, taste tests for quinine may be a biomarker for CRSwNP, and topical quinine has therapeutic potential as a stimulant of innate defenses.
气道中的苦味（T2R）和甜味（T1R）受体在先天免疫防御中很重要，一种 T2R（T2R38）的味觉受体功能的变化与慢性鼻-鼻窦炎（CRS）的疾病状态和严重程度相关。奎宁是一种苦味化合物，是几种也在鼻-鼻窦细胞上表达的 T2R 的激动剂，但不是 T2R38 的激动剂。由于这种特性，奎宁可能会刺激气道中的先天免疫防御机制，而奎宁感知的功能差异可能反映了 CRS 的疾病状态。
前瞻性地从 CRS 患者和非 CRS 对照受试者中收集人口统计学和味觉强度数据。还从接受鼻科手术的患者中收集鼻-鼻窦组织，并在气液界面（ALI）上培养。评估对奎宁刺激的一氧化氮（NO）产生和纤毛摆动频率的动态调节。
奎宁在 ALI 培养物中可靠地增加了纤毛摆动频率和 NO 产生，这种方式与 T2R 激活一致（<0.01）。在 328 名 CRS 患者和 287 名对照受试者中进行了奎宁味觉强度评定，结果表明，鼻息肉（CRSwNP）患者的奎宁味觉强度评定明显低于对照受试者。
奎宁通过增加纤毛摆动频率和以与 T2R 激活一致的方式刺激 NO 产生来刺激气道先天免疫防御。味觉强度评定中观察到患者对奎宁的敏感性存在差异，味觉上的奎宁“不敏感”与 CRSwNP 状态相关。因此，奎宁味觉测试可能是 CRSwNP 的生物标志物，局部奎宁具有作为先天防御刺激物的治疗潜力。
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