Zimmer J A, Lipton J M
Peptides. 1981 Winter;2(4):413-7. doi: 10.1016/s0196-9781(81)80097-6.
Central administration of ACTH (1-24) reduces fever in normal rabbits in doses that have no effect on afebrile body temperature. Previous experimental and clinical reports indicate that peripheral administration of both ACTH and corticosteroids reduces fever, and since central injection of corticosteroids can also lower fever it might be that the antipyretic effect of intracerebroventricular (ICV) ACTH (1-24) is due to adrenal stimulation. To learn whether this endogenous central peptide can produce antipyresis independently, ACTH (1-24) was injected ICV in bilaterally adrenalectomized (ADX) rabbits made febrile by IV injections of leukocytic pyrogen (LP). ACTH (250 ng) given ICV reduced fever in these animals and had a slight hypothermic effect when given to the same rabbits when they were afebrile. Doses of 25-75 ng reduced fever without influencing normal body temperature. Intravenous injections of ACTH (2.5 micrograms) also lowered fever caused by IV LP in ADX rabbits. The present findings raise the possibility that release of endogenous central ACTH, and perhaps entry into the brain of circulating ACTH, the release of which is known to increase in fever, limits the magnitude of the febrile response by influencing central temperature controls.
促肾上腺皮质激素（1 - 24）的中枢给药可降低正常家兔的体温，而这些剂量对正常体温并无影响。先前的实验和临床报告表明，促肾上腺皮质激素和皮质类固醇的外周给药均可降低体温，并且由于皮质类固醇的中枢注射也可降低体温，所以脑室内（ICV）注射促肾上腺皮质激素（1 - 24）的解热作用可能是由于肾上腺受到刺激所致。为了了解这种内源性中枢肽是否能独立产生解热作用，将促肾上腺皮质激素（1 - 24）脑室内注射到双侧肾上腺切除（ADX）的家兔体内，这些家兔通过静脉注射白细胞致热原（LP）而发热。脑室内注射250 ng促肾上腺皮质激素（1 - 24）可降低这些动物的体温，并且在这些家兔不发热时给予相同剂量可产生轻微的体温过低效应。25 - 75 ng的剂量可降低体温而不影响正常体温。静脉注射2.5微克促肾上腺皮质激素也可降低ADX家兔静脉注射LP所引起的发热。目前的研究结果提出了一种可能性，即内源性中枢促肾上腺皮质激素的释放，以及或许循环中的促肾上腺皮质激素进入大脑（已知其在发热时释放会增加），通过影响中枢体温调节来限制发热反应的程度。
