Decreased corticosensitivity in quiescent Crohn's disease: an ex vivo study using whole blood cell cultures.
Decreased corticosensitivity in quiescent Crohn's disease: an ex vivo study using whole blood cell cultures.
复制标题
静止期克罗恩病的皮质敏感性降低：使用全血细胞培养物的离体研究。
DOI：
10.1023/a:1026644711530
复制
发表时间：
1999
影响因子：
3.1
通讯作者：
Belaiche,J
中科院分区：
文献类型：
--
作者：
Franchimont,D;Louis,E;Dupont,P;Vrindts-Gevaert,Y;Dewe,W;Chrousos,G;Geenen,V;Belaiche,J
皮质敏感性通过改变靶细胞对内源性和/或外源性糖皮质激素的反应来影响炎症反应的程度和持续时间。事实上，在克罗恩病患者中观察到对糖皮质激素的不同临床反应，提示这些受试者的皮质激素敏感性程度不同。本研究的目的是比较静止期克罗恩病患者与健康人（HS）的皮质敏感性。研究了19例静止期克罗恩病和14例HS患者;所有患者均停用类固醇至少6个月; 19例患者中有7例为皮质类固醇依赖型（CSD），在研究期间接受非糖皮质激素免疫抑制剂治疗。皮质敏感性通过用递增浓度（10- 9至10 - 6 M）的地塞米松处理全血细胞培养物中LPS诱导的细胞因子分泌的抑制来测量。用特异性免疫分析法检测肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1 β（IL-1β），克罗恩病患者地塞米松介导的TNF-α（P <0.01）、IL-6（P < 0.001）和IL-1β（P < 0.01）的抑制作用明显低于健康受试者，地塞米松剂量-反应曲线右移。CSD和非CSD患者的基础和LPS刺激的三种细胞因子分泌无显著差异，两个亚组患者的地塞米松介导的细胞因子抑制程度相似。我们的结论是，克罗恩病患者的白细胞皮质敏感性显著降低，这可能与特定的遗传/体质背景有关，和/或由于炎症相关的内分泌和/或免疫因素而获得。
Corticosensitivity influences the degree and theduration of an inflammatory reaction by altering targetcell responses to endogenous and/or exogenousglucocorticoids. Indeed, different clinical responses to glucocorticoids have been observed amongpatients with Crohn's disease, suggesting differentdegrees of corticosensitivity in these subjects. Thepurpose of this study was to compare thecorticosensitivity of patients with quiescent Crohn's disease tothat of healthy subjects (HS). Nineteen patients withquiescent Crohn's disease and 14 HS were studied; allpatients were steroid-free for at least six months; 7 of the 19 were corticosteroid-dependent (CSD)and treated with nonglucocorticoid immunosuppressants atthe time of the study. Corticosensitivity was measuredby the inhibition of LPS-induced cytokine secretion in whole blood cell cultures treatedwith increasing concentrations (10-9to10-6M) of dexamethasone. Tumor-necrosisfactor-α (TNF-α), interleukin-6 (IL-6), andinterleukin-1β (IL-1β) were measured using specific immunoassays.Crohn's disease patients had a markedly decreaseddexamethasone-mediated inhibition of TNF-α (P <0.01), IL-6 (P < 0.001), and IL-1β (P < 0.01) compared to healthy subjects, with a shift ofthe dexamethasone dose-response curve to the right. Nosignificant differences in the basal and LPS-stimulatedsecretion of the three cytokines were observed between CSD and non-CSD patients, and bothsubgroups of patients had similar degrees ofdexamethasone-mediated cytokine inhibition. We concludethat patients with Crohn's disease have a significantdecrease in the corticosensitivity of their leukocytes.This may be related to a specific genetic/constitutionalbackground and/or could be acquired, due toinflammation-related endocrine and/or immunefactors.