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首页> 外文期刊>Inflammatory bowel diseases >Regulatory role of the pituitary-adrenal axis in experimental colitis: effect of adrenalectomy on the clinical course and the TH1/TH2 immune profile.
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Regulatory role of the pituitary-adrenal axis in experimental colitis: effect of adrenalectomy on the clinical course and the TH1/TH2 immune profile.

机译：垂体-肾上腺轴在实验性结肠炎中的调节作用：肾上腺切除术对临床过程和TH1 / TH2免疫特性的影响。

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BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in modulating immune reactions in inflammatory bowel disease. Our aim was to assess the role of the HPA axis in the pathogenesis of immunomediated colitis in mice. METHODS: Trinitrobenzene sulfonic acid (TNBS) colitis was induced in Balb/c mice. Sham operation (sham+TNBS) or bilateral adrenalectomy (Adex+TNBS) was performed 3 days later. Control groups underwent adrenalectomy without colitis induction (Adex) or were untreated [naive mice (Naive)]. Mice were monitored for survival, weight loss, and macroscopic and microscopic scores of colitis. FACS analysis of CD4, CD8, natural killer T lymphocytes, and serum levels of adrenocorticotropic hormone (ACTH), corticosterone (CS), interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and IL-1beta were measured. Production of prostaglandin E2 (PGE2) and binding capacity to glucocorticoid receptor (GR) in colonic mucosa were also assessed. RESULTS: By day 7 following induction ofcolitis there was a marked increase in ACTH and CS levels in the colitis as compared with the control group (86 +/- 6.5 pg/mL and 16 +/- 1.9 pg/mL, and 23.3 +/- 2 pg/mL and 2.8 +/- 0.8 pg/mL, respectively). There was a decrease in ACTH and CS levels by day 28 in the colitis group, but the levels were still significantly higher than the levels in controls. Adrenalectomy markedly exacerbated colitis. The macroscopic and microscopic scores increased from 2.79 +/- 0.03 and 2.0 +/- 0.1 in the sham+TNBS group to 3.3 +/- 0.3 and 3.2 +/- 0.3 in the Adex+TNBS group. Survival and weight loss correlated with these differences. A significant increase in IL-10, IFN-gamma, and PGE2 was noted in the Adex+TNBS group compared with the sham+TNBS group. Splenic CD4 lymphocytes decreased in the sham+TNBS and Adex+TNBS groups as compared with control groups (Adex and naive). The CD8/CD4 ratio was significantly higher in the Adex+TNBS compared with the sham+TNBS group. Colitis also caused a significant decrease in the specific binding capacity of labeled dexamethasone to colonic mucosa. CONCLUSIONS: TNBS induced colitis activated the HPA axis and reduced the sensitivity of the inflamed mucosa to circulating glucocorticoids. Adrenalectomy markedly exacerbated TNBS-induced colitis. The effect was associated with changes in the peripheral CD8/CD4 ratio and with a TH1 cytokine shift. Our results suggest that adrenocortical hormones play an important role in the regulation of the immune system in experimental colitis.
机译：背景：下丘脑-垂体-肾上腺（HPA）轴在调节炎症性肠病的免疫反应中起重要作用。我们的目的是评估HPA轴在小鼠免疫介导的结肠炎发病机理中的作用。方法：在Balb / c小鼠中诱发三硝基苯磺酸（TNBS）结肠炎。 3天后进行假手术（sham + TNBS）或双侧肾上腺切除术（Adex + TNBS）。对照组接受不进行结肠炎诱导的肾上腺切除术（Adex）或未接受治疗的组[幼稚小鼠（Naive）]。监测小鼠的存活，体重减轻以及结肠炎的宏观和微观得分。 FACS分析CD4，CD8，自然杀伤性T淋巴细胞以及促肾上腺皮质激素（ACTH），皮质酮（CS），干扰素-γ（IFN-γ），白介素10（IL-10）和IL-1beta的血清水平测量。还评估了前列腺粘膜中前列腺素E2（PGE2）的产生以及与糖皮质激素受体（GR）的结合能力。结果：到结肠炎诱发后第7天，与对照组相比，结肠炎中ACTH和CS水平显着增加（86 +/- 6.5 pg / mL和16 +/- 1.9 pg / mL，和23.3 + / -分别为2 pg / mL和2.8 +/- 0.8 pg / mL）。在结肠炎组中，到第28天时ACTH和CS水平有所降低，但该水平仍显着高于对照组。肾上腺切除术明显加剧了结肠炎。宏观和微观得分从假+ TNBS组的2.79 +/- 0.03和2.0 +/- 0.1增加到Adex + TNBS组的3.3 +/- 0.3和3.2 +/- 0.3。存活率和体重减轻与这些差异相关。与假手术+ TNBS组相比，Adex + TNBS组的IL-10，IFN-γ和PGE2明显增加。与对照组（Adex和天真）相比，sham + TNBS和Adex + TNBS组的脾CD4淋巴细胞减少。与假手术+ TNBS组相比，Adex + TNBS中的CD8 / CD4比明显更高。结肠炎还导致标记的地塞米松与结肠粘膜的特异性结合能力显着降低。结论：TNBS引起的结肠炎激活了HPA轴并降低了发炎的粘膜对循环糖皮质激素的敏感性。肾上腺切除术明显加剧了TNBS引起的结肠炎。这种作用与外周CD8 / CD4比值的变化以及TH1细胞因子的变化有关。我们的结果表明，肾上腺皮质激素在实验性结肠炎的免疫系统调节中起着重要作用。

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