Swain M G, Appleyard C B, Wallace J L, Maric M
Liver Unit, University of Calgary, Alberta, Canada.
J Hepatol. 1997 Feb;26(2):361-8. doi: 10.1016/s0168-8278(97)80053-0.
We investigated the role of TNF-alpha in inflammation-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis in rats with cholestasis due to bile duct resection.
Acute inflammation was induced in bile duct or sham resected rats by subcutaneous injection of carrageenan and HPA axis activation was determined by measuring plasma ACTH and corticosterone levels in the absence or presence of TNF-alpha inhibition.
Bile duct resected rats had a 2.4-fold elevation in basal circulating TNF-alpha levels compared to sham resected and unoperated controls. Acute inflammation induced by carrageenan injection resulted in a significant increase in plasma ACTH and corticosterone levels in bile duct resected and control rats in the absence of significant changes in plasma TNF-alpha levels. However, bile duct resected rats demonstrated blunted ACTH release coupled with augmented corticosterone secretion in response to carrageenan administration compared to control rats. Inhibition of TNF-alpha activity by pretreating rats with a specific TNF-antiserum or pentoxifylline did not alter inflammation-induced ACTH secretion in bile duct resected or control rats, or corticosterone secretion in control rats. However, anti-TNF treatments significantly attenuated the inflammation-induced rise in plasma corticosterone in bile duct resected rats.
These results indicate that inflammation in rats with biliary obstruction is associated with blunted ACTH release coupled with augmented glucocorticoid secretion facilitated by TNF-alpha. Furthermore, these results suggest that what have been previously considered as low level elevations in circulating TNF-alpha levels can facilitate adrenal glucocorticoid secretion during the inflammatory response.
我们研究了肿瘤坏死因子-α（TNF-α）在胆管切除所致胆汁淤积大鼠炎症诱导的下丘脑-垂体-肾上腺（HPA）轴激活中的作用。
通过皮下注射角叉菜胶在胆管切除或假手术大鼠中诱导急性炎症，并在不存在或存在TNF-α抑制的情况下，通过测量血浆促肾上腺皮质激素（ACTH）和皮质酮水平来确定HPA轴的激活情况。
与假手术和未手术的对照组相比，胆管切除大鼠的基础循环TNF-α水平升高了2.4倍。角叉菜胶注射诱导的急性炎症导致胆管切除大鼠和对照大鼠血浆ACTH和皮质酮水平显著升高，而血浆TNF-α水平无显著变化。然而，与对照大鼠相比，胆管切除大鼠在给予角叉菜胶后ACTH释放减弱，同时皮质酮分泌增加。用特异性TNF抗血清或己酮可可碱预处理大鼠抑制TNF-α活性，并未改变胆管切除大鼠或对照大鼠炎症诱导的ACTH分泌，也未改变对照大鼠的皮质酮分泌。然而，抗TNF治疗显著减弱了胆管切除大鼠炎症诱导的血浆皮质酮升高。
这些结果表明，胆道梗阻大鼠的炎症与ACTH释放减弱以及TNF-α促进的糖皮质激素分泌增加有关。此外，这些结果表明，以前被认为是循环TNF-α水平的低水平升高，在炎症反应期间可促进肾上腺糖皮质激素分泌。
