title: Does IL-6 release ACTH by exerting a direct effect in the rat anterior pituitary.
abstract: Adult male rats were used to determine whether high circulating levels of the pro-inflammatory cytokine interleukin-6 (IL-6) were capable of releasing ACTH independently of endogenous corticotropin-releasing factor (CRF). On one hand, CRF antibodies or a potent CRF antagonist significantly decreased, but did not totally abolish the ACTH response to the intravenous(i.v.) injection of recombinant rat IL-6. These results suggest that this cytokine might act either directly on the pituitary, or can release ACTH through mechanisms that do not involve CRF. On the other hand, the CRF antagonist or antibodies significantly (but not totally) blocked ACTH secretion due to the i.v. injection of endotoxin (LPS) while enhancing the ability of this immune stimulus to increase serum IL-6 concentrations. These results indicate that during endotoxemia, even very elevated circulating IL-6 concentrations were notable to release large amounts of ACTH in the absence of CRF drive. These data also illustrate the ability of a CRF antagonist or CRF antibodies to significantly augment IL-6 secretion,which indicates an inhibitory influence of the endogenous peptide in the paradigm we used.As comparable findings were obtained in adrenal-intact and adrenalectomized rats, they suggest that endogenous CRF is involved in the IL-6 response to LPS independently of circulating corticosteroids or other adrenal factors.
authors.affiliation: The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CA 92037, USA. crivier@salk.edu
authors.forename: C
authors.initials: C
authors.lastname: Rivier
mesh_terms: D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D006727:Hormone Antagonists / Q000008:administration & dosage; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014667:Vasopressins / Q000008:administration & dosage
chemical_list: D006727:Hormone Antagonists; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C120841:astressin B; C433788:lipopolysaccharide, E. coli O26-B6; D014667:Vasopressins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone