Interleukin-6 stimulates the hypothalamus-pituitary-adrenocortical axis in man

J Clin Endocrinol Metab. 1994 Oct;79(4):1212-4. doi: 10.1210/jcem.79.4.7962296.


A recent study in humans, animal studies, and in vitro data have suggested that interleukin-6 (IL-6) stimulates the secretory activity of the hypothalamus-pituitary-adrenocortical (HPA) axis. In a phase II study, one female and six male patients with metastatic renal cell carcinoma received IL-6 to evaluate a possible antitumor effect of IL-6. This offered the possibility of investigating the influence of IL-6 on the HPA axis in man. The subjects were studied 1 day before, on day 1, and on day 21 of IL-6 therapy (150 micrograms administered sc every day at 0900 h). Blood samples were taken at 0900, 1100, 1300, 1600, and 2000 h the day before, on day 1 of IL-6 therapy, 24 h after the first IL-6 injection, and on day 21 of IL-6 treatment. Plasma ACTH and cortisol levels promptly followed the rise of IL-6, which peaked 4 h after administration. They were significantly (P < 0.05) higher at 1100 and 1300 h on day 1 of IL-6 therapy compared with the corresponding plasma levels the day before IL-6 treatment. Cortisol concentrations remained significantly increased at 1600 and 2000 h after IL-6 administration. Twenty-four hours after the first IL-6 administration, IL-6, ACTH, and cortisol levels had reached preinjection values. Although plasma cortisol levels were similar on days 1 and 21, ACTH levels were lower on day 21 (than on day 1), but significantly elevated at 1100 h compared with levels on the day before the first IL-6 injection. Results confirming the very recent data of another study demonstrate a stimulating effect of IL-6 on the HPA axis in man. They support the notion that IL-6 is one of the cytokines involved in the interaction between the immune system and the HPA axis.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex / drug effects
  • Adrenocorticotropic Hormone / blood
  • Circadian Rhythm
  • Female
  • Humans
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / drug effects*
  • Interleukin-6 / adverse effects
  • Interleukin-6 / pharmacology*
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Pituitary-Adrenal System / drug effects*
  • Recombinant Proteins


  • Interleukin-6
  • Recombinant Proteins
  • Adrenocorticotropic Hormone
  • Hydrocortisone