Henriksson G, Norlander T, Forsgren J, Stierna P
Department of Clinical Sciences, Karolinska Institute, Huddinge University Hospital, Sweden.
Am J Rhinol. 2001 Jan-Feb;15(1):1-8. doi: 10.2500/105065801781329446.
The effects of a topically applied corticosteroid, budesonide, on the expression of glucocorticoid receptor (GR) mRNA and regulation of pro-inflammatory cytokine patterns in patients with nasal polyps were evaluated. All patients were eligible for surgical polypectomy, and a majority of them had been treated with nasal steroids. Patients were given 400 microg b.i.d. (group A, n = 11), 200 microg b.i.d. (group B, n = 10), or no treatment (group C, n = 15) during two months before polypectomy. Morning serum cortisol was analyzed on the day of surgery. Surgically removed polyps were taken for analysis of GR mRNA expression by solution hybridization. Remaining tissue was cryostat-sectioned, whereafter quantification of the cytokines interleukin 1beta, interleukin 2, interleukin 4, interleukin 5, interleukin 6, interleukin 10, tumor necrosis factor alpha, and interferon gamma was made by immunohistochemistry and digitized image analysis. No significant differences among the three groups were found for any of the parameters investigated.
nasal polyps do not respond with down-regulation of GR mRNA or cytokines following topical corticosteroid treatment. The proposed corticosteroid resistance may be inherent, or induced by a change of local tissue bioavailability.
评估局部应用皮质类固醇布地奈德对鼻息肉患者糖皮质激素受体(GR)mRNA表达及促炎细胞因子模式调节的影响。所有患者均符合手术息肉切除术条件,且大多数患者曾接受鼻用类固醇治疗。在息肉切除术前行两个月的治疗,A组(n = 11)患者每日两次给予400μg,B组(n = 10)患者每日两次给予200μg,C组(n = 15)不接受治疗。手术当天分析晨血清皮质醇。手术切除的息肉用于通过溶液杂交分析GR mRNA表达。剩余组织进行冷冻切片,然后通过免疫组织化学和数字化图像分析对细胞因子白细胞介素1β、白细胞介素2、白细胞介素4、白细胞介素5、白细胞介素6、白细胞介素10、肿瘤坏死因子α和干扰素γ进行定量。在所研究的任何参数中,三组之间均未发现显著差异。
局部应用皮质类固醇治疗后,鼻息肉不会出现GR mRNA或细胞因子的下调反应。所提出的皮质类固醇抵抗可能是固有的,或由局部组织生物利用度的改变所诱导。