Induction of adrenocorticotropic hormone release by interleukin-6 in vivo and in vitro.
Recent reports show that cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF) and intravenously administered interleukin-6 (IL-6) stimulate adrenocorticotropic hormone (ACTH) release. Both IL-1 and TNF are known to be potent inducers of IL-6, a monokine produced by activated monocytes and folliculo-stellate cells of the pituitary gland and released from the hypothalamus. To determine the site(s) of action of IL-6 in the control of ACTH release, we injected human recombinant IL-6 into the third brain ventricle (3V) of freely moving, conscious male rats and measured ACTH by RIA. Both 0.05 pmole and 0.25 pmole doses of IL-6 were ineffective to change plasma ACTH in comparison to the values in controls. The maximal IL-6 dose tested of 1.25 pmole increased plasma ACTH within 15 min and the response lasted over 180 min. The effects of IL-6 on plasma ACTH were only partially paralleled by increased rectal temperature which suggests that hypothalamic temperature regulating centers were independent of these actions. To evaluate a possible direct effect on the pituitary, IL-6 was incubated in vitro with hemipituitaries under an atmosphere of 95% O2/5% CO2. After 1 hr of incubation IL-6 failed to cause any change in the secretion of ACTH throughout a concentration range of 10(-15) to 10(-9) M. Increased ACTH secretion into the incubation medium was found only with 10(-13) M IL-6 after a 2-hr incubation. The results support a possible role for IL-6 at both hypothalamic and/or pituitary levels to stimulate ACTH release.
Lyson
K
K
Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235-9040.
McCann
S M
SM
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D015850:Interleukin-6; D000324:Adrenocorticotropic Hormone