Franchimont D, Bouma G, Galon J, Wolkersdörfer G W, Haidan A, Chrousos G P, Bornstein S R
Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Gastroenterology. 2000 Dec;119(6):1560-8. doi: 10.1053/gast.2000.20235.
BACKGROUND & AIMS: Proper adrenal glucocorticoid secretion is crucial in the course of inflammatory diseases. However, the function and structure of the adrenal glands have not been examined in inflammatory bowel diseases.
After induction of trinitrobenzene sulfonic acid (TNBS) colitis in SJL/J mice, plasma hormone and cytokine levels were measured, adrenal structure was analyzed by immunohistochemistry and electron microscopy, and adrenal cytokine/cytokine receptor expression were studied by RNase protection.
Adrenals of colitic animals were enlarged and hypervascularized. These animals had a marked increase in plasma corticosterone levels during the course of colitis (270 +/- 34 vs. 16 +/- 11 ng/mL; P < 0.0001) but only a modest elevation of their concurrent adrenocorticotropin levels (57 +/- 13 vs. 29 +/- 9 pmol/L; NS). On electron microscopy, adrenocortical cells showed ultrastructural signs of marked stimulation, and intra-adrenal lymphocytes were frequently found in direct contact with these cells. Concurrent plasma levels of interleukin (IL)-6, the major cytokine activating the hypothalamic-pituitary-adrenal axis, were markedly increased (495 +/- 131 vs. 20 +/- 1.5 pg/mL; P < 0.0001), and this cytokine directly stimulated corticosterone secretion by adrenocortical cells in vitro. Intra-adrenal expression of IL-6 in animals with colitis was increased 80-fold, and the IL-6 receptor subunits IL-6R alpha and gp130 were present in the adrenal cells. Treatment of animals with neutralizing anti-IL-6 antibody reduced the TNBS-induced growth and activation of the adrenal cortices.
Colitis is associated with a profound stimulation of adrenocortical cell function and glucocorticoid release. Direct immune-adrenal interactions seem to contribute to this activation of the adrenal glands during colitis.
肾上腺糖皮质激素的正常分泌在炎症性疾病过程中至关重要。然而，尚未在炎症性肠病中对肾上腺的功能和结构进行研究。
在SJL/J小鼠中诱导三硝基苯磺酸（TNBS）结肠炎后，测量血浆激素和细胞因子水平，通过免疫组织化学和电子显微镜分析肾上腺结构，并通过核糖核酸酶保护法研究肾上腺细胞因子/细胞因子受体表达。
结肠炎动物的肾上腺增大且血管增多。这些动物在结肠炎病程中血浆皮质酮水平显著升高（270±34 vs. 16±11 ng/mL；P<0.0001），但其同时的促肾上腺皮质激素水平仅适度升高（57±13 vs. 29±9 pmol/L；无显著性差异）。电子显微镜检查显示，肾上腺皮质细胞呈现明显受刺激的超微结构迹象，且肾上腺内淋巴细胞常与这些细胞直接接触。同时，激活下丘脑 - 垂体 - 肾上腺轴的主要细胞因子白细胞介素（IL）-6的血浆水平显著升高（495±131 vs. 20±1.5 pg/mL；P<0.0001），并且该细胞因子在体外直接刺激肾上腺皮质细胞分泌皮质酮。结肠炎动物肾上腺内IL-6的表达增加了80倍，肾上腺细胞中存在IL-6受体亚基IL-6Rα和gp130。用中和性抗IL-6抗体治疗动物可减少TNBS诱导的肾上腺皮质生长和激活。
结肠炎与肾上腺皮质细胞功能的深度刺激和糖皮质激素释放有关。直接的免疫 - 肾上腺相互作用似乎在结肠炎期间促成了肾上腺的这种激活。
