Sharp B M, Matta S G, Peterson P K, Newton R, Chao C, Mcallen K
Endocrine-Neuroscience Research Lab, Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota.
Endocrinology. 1989 Jun;124(6):3131-3. doi: 10.1210/endo-124-6-3131.
Tumor necrosis factor-alpha (TNF) and interleukin-1 beta (IL-1) are secreted by activated monocytes and other immune cells. Since IL-1 has been shown to elevate rat plasma ACTH and both of these cytokines induce similar acute-phase responses, the present studies of TNF were undertaken to characterize the ACTH response to this immune cell product. Human rTNF, administered iv at doses (100-1000 ng) which failed to affect blood pressure, food consumption or prolactin levels, resulted in significant peak elevations of rat plasma ACTH within 20 min (mean +/- SE 304 +/- 94 and 958 +/- 128 pg/ml for 100 and 1000 ng, respectively, compared to 53 +/- 16 pg/ml for vehicle). rTNF from two different sources produced similar elevations of ACTH as an equivalent amount of rIL-1. TNF failed to affect cultured anterior pituicytes, and it did not modify the response to CRF. When administered into the upper third cerebroventricle, TNF 20 ng failed to affect ACTH levels whereas IL-1 30 ng raised ACTH to 638 +/- 79 pg/ml compared to 177 +/- 24 pg/ml for vehicle (p less than .001). Furthermore, intraparenchymal injection of IL-1, directly above the median eminence, elevated ACTH to 484 +/- 93 pg/ml; again, TNF was completely ineffective. Thus, TNF-alpha and IL-1 beta are both potent ACTH secretagogues with complementary modes of action; however, the proximate target of TNF action appears to be peripheral to the CNS and pituitary whereas that of IL-1 appears to be the median eminence.
肿瘤坏死因子-α（TNF）和白细胞介素-1β（IL-1）由活化的单核细胞和其他免疫细胞分泌。由于IL-1已被证明可升高大鼠血浆促肾上腺皮质激素（ACTH），且这两种细胞因子都能诱导相似的急性期反应，因此开展了本项关于TNF的研究，以表征对这种免疫细胞产物的ACTH反应。静脉注射人重组TNF（rTNF），剂量为100 - 1000 ng，该剂量未影响血压、食物摄入量或催乳素水平，但在20分钟内导致大鼠血浆ACTH显著峰值升高（100 ng和1000 ng时分别为平均±标准误304±94和958±128 pg/ml，而溶媒组为53±16 pg/ml）。来自两种不同来源的rTNF产生的ACTH升高与等量的rIL-1相似。TNF对培养的垂体前叶细胞无影响，也未改变对促肾上腺皮质激素释放因子（CRF）的反应。当注入第三脑室上部时，20 ng的TNF未影响ACTH水平，而30 ng的IL-1使ACTH升高至638±79 pg/ml，相比之下溶媒组为177±24 pg/ml（p < 0.001）。此外，在正中隆起上方脑实质内注射IL-1使ACTH升高至484±93 pg/ml；同样，TNF完全无效。因此，TNF-α和IL-1β都是有效的ACTH促分泌素，作用方式互补；然而，TNF作用的直接靶点似乎在中枢神经系统和垂体之外，而IL-1的靶点似乎是正中隆起。
