The ratio of 11β-hydroxysteroid dehydrogenase 1/11β-hydroxysteroid dehydrogenase 2 predicts glucocorticoid response in nasal polyps.

Abstract

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.