Interleukin-6 stimulates the hypothalamus-pituitary-adrenocortical axis in man.
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.
Department of Internal Medicine, University of Ulm, Germany.
E
E
Späth-Schwalbe
J
J
Born
H
H
Schrezenmeier
S R
SR
Bornstein
P
P
Stromeyer
S
S
Drechsler
H L
HL
Fehm
F
F
Porzsolt
D000302:Adrenal Cortex / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000097:blood; D002940:Circadian Rhythm; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D015850:Interleukin-6 / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011994:Recombinant Proteins
D015850:Interleukin-6; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone