RECOMBINANT INTERLEUKIN-6 ACTIVATES THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN HUMANS
RECOMBINANT INTERLEUKIN-6 ACTIVATES THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN HUMANS
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DOI：
10.1210/jc.77.6.1690
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发表时间：
1993-12-01
影响因子：
5.8
通讯作者：
WEBER, JS
中科院分区：
文献类型：
--
作者：
MASTORAKOS, G;CHROUSOS, GP;WEBER, JS
The inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 alpha and -beta (IL-1 alpha and -beta), and IL-6 can activate the hypothalamic-pituitary-adrenal (HPA) axis. Tumor necrosis factor-alpha and IL-I have been tested in both experimental animals and humans, but their administration has been limited by significant toxicity, mainly severe hypotension. IL-6, on the other hand, has demonstrated modest toxicity in animals. We evaluated the ability of recombinant IL-6 to stimulate the human HPA axis in patients with cancer and a good performance status, who received daily morning sc injections of 30 mu g/kg IL-6 for 7 consecutive days, during the course of a phase I trial. IL-6 caused impressively marked and prolonged elevations of plasma ACTH and cortisol on the first day and blunted ACTH responses on the seventh day of treatment, perhaps as a result of increased baseline cortisol levels. The overall cortisol response, however, on the seventh day was of similar magnitude, suggesting that a new equilibrium in the feedback regulation of the HPA axis occurs with chronic IL-6 administration. The toxic effects of IL-6 were modest, suggesting that it might be useful for clinical testing of the HPA axis, as an alternative to the insulin tolerance test.
