Sweep C G, van der Meer M J, Hermus A R, Smals A G, van der Meer J W, Pesman G J, Willemsen S J, Benraad T J, Kloppenborg P W
Department of Medicine, St. Radboud Hospital, University of Nijmegen, The Netherlands.
Endocrinology. 1992 Mar;130(3):1153-64. doi: 10.1210/endo.130.3.1311230.
It has been shown that acute administration of interleukin-1 (IL-1) to rats elicits a transitory increase in plasma ACTH and corticosterone (B) levels. To investigate the effects of chronic administration of IL-1 on plasma ACTH and B levels, in the present study rats were equipped with Alzet osmotic minipumps loaded with either IL-1 (delivery rate 0.5, 2.0, or 4.0 micrograms/24 h, ip, for 1 week) or saline. At the end of the treatment the rats were decapitated, the adrenals were weighed, and the in vitro release of beta-endorphin (beta E) by the anterior pituitary and that of B by the adrenal gland were measured. Continuous administration of 2.0 and 4.0 micrograms IL-1/24 h resulted in a persistent increase in plasma ACTH and B concentrations compared to the levels in saline-infused rats, with peak levels on the first day of administration. In addition, adrenal weights of IL-1 rats were significantly higher than those of saline rats. The 4.0-micrograms IL-1/day in vivo treatment induced an increase in spontaneous in vitro secretion of beta E and B, while the in vitro responses of the pituitary (to CRF) and the adrenal (to ACTH) of animals treated in vivo with IL-1 were significantly diminished. IL-1 at a dose of 0.5 microgram failed to affect plasma ACTH and B values, adrenal weight, and in vitro beta E and B secretion. Chronic infusion of rats with 4.0 micrograms IL-1/day induced prolonged fever, whereas at lower doses of IL-1 (2.0 and 0.5 micrograms), temperatures were elevated only on the first 2 days of infusion. IL-1 at doses of 2.0 and 4.0 micrograms/day induced suppression of body weight gain on the first 2 days of the treatment period compared to saline treatment. Plasma norepinephrine and/or epinephrine concentrations were raised only on day 1 of the 2.0- and 4.0-micrograms IL-1 experiments. Thus, the observed effects of IL-1 on the hypothalamo-pituitary-adrenal axis probably do not result merely from stress induced by the treatment. Taken together, our data show the potential of IL-1 to induce a dose-dependent and long term activation of the pituitary-adrenal axis.
已经表明，对大鼠急性给予白细胞介素 -1（IL -1）会引起血浆促肾上腺皮质激素（ACTH）和皮质酮（B）水平的短暂升高。为了研究慢性给予IL -1对血浆ACTH和B水平的影响，在本研究中，给大鼠植入Alzet渗透微型泵，其中装载IL -1（给药速率0.5、2.0或4.0微克/24小时，腹腔注射，持续1周）或生理盐水。在治疗结束时，将大鼠断头，称量肾上腺重量，并测量垂体前叶β-内啡肽（βE）的体外释放以及肾上腺皮质酮（B）的体外释放。与注入生理盐水的大鼠相比，持续给予2.0和4.0微克IL -1/24小时导致血浆ACTH和B浓度持续升高，在给药第一天达到峰值水平。此外，IL -1处理组大鼠的肾上腺重量显著高于生理盐水处理组大鼠。每天4.0微克IL -1的体内处理诱导体外βE和B的自发分泌增加，而体内用IL -1处理的动物垂体（对促肾上腺皮质激素释放因子（CRF））和肾上腺（对促肾上腺皮质激素（ACTH））的体外反应显著减弱。0.5微克剂量的IL -1未能影响血浆ACTH和B值、肾上腺重量以及体外βE和B分泌。每天给大鼠慢性输注4.0微克IL -1会引起长时间发热，而在较低剂量的IL -1（2.0和0.5微克）时，仅在输注的前2天体温升高。与生理盐水处理相比，每天2.0和4.0微克剂量的IL -1在治疗期的前2天诱导体重增加受到抑制。仅在2.0和4.0微克IL -1实验的第1天血浆去甲肾上腺素和/或肾上腺素浓度升高。因此，观察到的IL -1对下丘脑 - 垂体 - 肾上腺轴的影响可能不仅仅是由治疗引起的应激导致的。综上所述，我们的数据表明IL -1具有诱导垂体 - 肾上腺轴剂量依赖性和长期激活的潜力。
