Mastorakos G, Chrousos G P, Weber J S
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
J Clin Endocrinol Metab. 1993 Dec;77(6):1690-4. doi: 10.1210/jcem.77.6.8263159.
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-1 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 micrograms/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.
炎性细胞因子，如肿瘤坏死因子-α、白细胞介素-1α和-1β（IL-1α和-1β）以及IL-6，可激活下丘脑-垂体-肾上腺（HPA）轴。肿瘤坏死因子-α和IL-1已在实验动物和人类中进行了测试，但其给药受到显著毒性的限制，主要是严重低血压。另一方面，IL-6在动物中表现出适度的毒性。在一项I期试验过程中，我们评估了重组IL-6刺激癌症患者且身体状况良好者的人HPA轴的能力，这些患者连续7天每天早上皮下注射30微克/千克IL-6。IL-6在治疗第一天使血浆促肾上腺皮质激素（ACTH）和皮质醇显著且持续升高，而在治疗第七天ACTH反应减弱，这可能是由于基线皮质醇水平升高所致。然而，第七天的总体皮质醇反应幅度相似，这表明长期给予IL-6会使HPA轴反馈调节出现新的平衡。IL-6的毒性作用较小，这表明它可能作为胰岛素耐量试验的替代方法，用于HPA轴的临床检测。
