{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T18:59:33Z","timestamp":1777921173478,"version":"3.51.4"},"reference-count":0,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2008,4,9]],"date-time":"2008-04-09T00:00:00Z","timestamp":1207699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2008,4,9]],"date-time":"2008-04-09T00:00:00Z","timestamp":1207699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroendocrinology"],"abstract":"<jats:p>Interleukin-6 (IL-6), the main circulating cytokine, is putatively a major mediator of the effects of the immune system on several endocrine axes and intermediate metabolism. We performed dose-response studies of recombinant human IL\u00b76 on pituitary hormone secretion in 15 healthy male volunteers, using 5 single, escalating subcutaneous doses of IL-6 (0.1, 0.3, 1.0, 3.0 and 10.0 \u00b5g\/kg body weight), each in 3 volunteers. We measured resting metabolic rate (RMR) with indirect calorimetry and plasma anterior pituitary hormones and vasopressin (AVP) at baseline and half-hourly over 4 h after the injection. All doses examined were tolerated well and produced no significant adverse effects. Dose-dependent RMR increases were observed in response to the 3.0- and 10.0-\u00b5g\/kg doses of IL-6, beginning at 60 min and slowly peaking between 180 and 240 min. Plasma adrenocorticotropic-hormone concentrations increased dramatically and dose-dependently in all the patients who received the 3.0- and 10.0-\u00b5g\/kg doses of IL-6, respectively, peaking to 150 and 255 pg\/ml at 60 min, and slowly returning to normal by 4 h. Corresponding plasma cortisol levels peaked dose-dependently between 90 and 150 min, but remained elevated throughout the sampling period. In contrast, the growth hormone (GH) dose-response was bell-shaped, with maximum (approximately 100-fold) stimulation achieved by 3.0 \u00b5g\/kg IL-6. Prolactin (PRL) showed a similar but less pronounced response pattern. Thyroid-stimulating hormone (TSH) dose-dependently and progressively decreased over the 240 min, while gonadotropins showed no clear-cut changes. In conclusion, subcutaneous IL-6 administration induced synchronized dose-dependent increases in the RMR and hypothalamic-pituitary-adrenal axis activity, suggesting that hypothalamic corticotropin-releasing hormone may mediate both of these functions in humans. IL-6 also acutely stimulated GH and PRL secretion and suppressed TSH secretion. The dose of 3.0 \u00b5g\/kg could be used safely in the study of patients with disturbances of the hypothalamic-pituitary unit or of thermogenesis.<\/jats:p>","DOI":"10.1159\/000127219","type":"journal-article","created":{"date-parts":[[2008,4,10]],"date-time":"2008-04-10T04:37:20Z","timestamp":1207802240000},"page":"54-62","source":"Crossref","is-referenced-by-count":169,"title":["Dose Effects of Recombinant Human lnterleukin-6 on Pituitary Hormone Secretion and Energy Expenditure"],"prefix":"10.1159","author":[{"given":"Constantine","family":"Tsigos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitris A.","family":"Papanicolaou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruby","family":"Defensor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constantine S.","family":"Mitsiadis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Kyrou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George P.","family":"Chrousos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2008,4,9]]},"container-title":["Neuroendocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/127219","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000127219","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T19:47:52Z","timestamp":1777664872000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000127219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,4,9]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1159\/000127219","archive":["Portico"],"relation":{},"ISSN":["0028-3835","1423-0194"],"issn-type":[{"value":"0028-3835","type":"print"},{"value":"1423-0194","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,4,9]]}}}