The DOI matches its Crossref record; 18 of the 23 references it cites were found in a registry or an index.
Dose-Dependent Effects of Recombinant Human Interleukin-6 on Glucose Regulation
Abstract
Inflammatory cytokines have metabolic actions that probably contribute to the general adaptation of the organism during infectious or inflammatory stress. To examine the effects of interleukin 6 (IL-6), the main circulating cytokine, on glucose metabolism in man, we performed dose-response studies of recombinant human IL-6 in normal volunteers. Increasing single doses of IL-6 (0.1, 0.3, 1.0, 3.0, and 10.0 mg/Kg BW) were injected sc in 15 healthy male volunteers (3 in each dose) after a 12-h fast. All IL-6 doses were tolerated well and produced no significant adverse effects. We measured the circulating levels of glucose, insulin, C-peptide, and glucagon at baseline and half-hourly over 4 h after the IL-6 injection. Mean peak plasma levels of IL-6 were achieved between 120 and 240 min and were 8, 22, 65, 290, and 4050 pg/mL, respectively, for the 5 doses. After administration of the 2 smaller IL-6 doses, we observed no significant changes in plasma glucose levels, which, because of continued fasting, decreased slightly over time. By 60 min after the 3 higher IL-6 doses, however, the decline in fasting blood glucose was arrested, and glucose levels increased in a dose-dependent fashion. The concurrent levels of plasma insulin and C-peptide were not affected by any IL-6 dose. In contrast, IL-6 caused significant increases in plasma glucagon levels, which peaked between 120 and 150 min after the IL-6 injection. In conclusion, sc IL-6 administration induced dose-dependent increases in fasting blood glucose, probably by stimulating glucagon release and other counteregulatory hormones and/or by inducing peripheral resistance to insulin action.
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“and causes hepatic and muscle insulin resistance in humans and in mice (39,55-60).”
From Expression of Mfn2, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [60]
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Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans.
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Self-citationSystemic cytokine response after major surgery
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Research works printed but not linked: 1
- Tsigos, 1997, Dose-effects of recombinant human interleukin-6 on anterior pituitary hormone secretion and thermogenesis., Neuroendocrinology, 48, 1212
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C-Reactive Protein, Interleukin 6, and Risk of Developing Type 2 Diabetes Mellitus
Pradhan, A. D. (2001) · JAMA · doi:10.1001/jama.286.3.327 · Cited by 4,433
“In this regard, substantial experimental evidence and more recent crosssectional data suggest that interleukin 6 (IL-6) and C-reactive protein (CRP), 2 sensitive physiological markers of subclinical systemic inflammation, are associated with hyperglycemia, insulin resistance, and overt type 2 DM.(8-15) Indeed, it rece…”
BackgroundHypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress
Tsigos, C., & Chrousos, G. P. (2002) · Journal of Psychosomatic Research · doi:10.1016/s0022-3999(02)00429-4 · Cited by 2,822
“Because increased hepatic gluconeogenesis is a characteristic feature of the stress response and because glucocorticoids induce insulin resistance, activation of the HPA axis may contribute to the poor control of diabetic patients during periods of emotional stress, or concurrently with inflammatory and other diseases…”
BackgroundSelf-citationEsposito, K., Nappo, F., Marfella, R., Giugliano, G., Giugliano, F., Ciotola, M., Quagliaro, L., Ceriello, A., & Giugliano, D. (2002) · Circulation · doi:10.1161/01.cir.0000034509.14906.ae · Cited by 1,961
Jung, U. J., & Choi, M. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15046184 · Cited by 1,971
“Hyperglycemia results in increased IL-6 levels [97], and treatment with IL-6 induces hyperglycemia and insulin resistance in humans [98].”
BackgroundAdipose tissue dysfunction in obesity, diabetes, and vascular diseases
Hajer, G. R., van Haeften, T. W., & Visseren, F. L. J. (2008) · European Heart Journal · doi:10.1093/eurheartj/ehn387 · Cited by 1,410
“given peripherally results in decreased insulin sensitivity in healthy males.(27) IL-6 upregulates vascular endothelial growth factor”
Background
Metadata
- Authors
- Tsigos, C., Papanicolaou, D. A., Kyrou, I., Defensor, R., Mitsiadis, C. S., & Chrousos, G. P.
- Affiliations
- National Institutes of Health (US)
- Hellenic National Center for Research, Prevention and Treatment of Diabetes Mellitus and its Complications (C.T., I.K.), Athens 106 75, Greece
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1997-12-01
- Volume
- 82
- Issue
- 12
- Pages
- 4167-4170
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2086682722
- Cited by
- 324
- References
- 23
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 8 · 2019: 5 · 2018: 17 · 2017: 10 · 2016: 11 · 2015: 8 · 2014: 21 · 2013: 9 · 2012: 16
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- interleukin-6, glucose regulation, glucagon, insulin, C-peptide, dose-response relationship, inflammatory cytokines, insulin resistance, fasting blood glucose
- MeSH terms
- Adult, Blood Glucose, C-Peptide, Dose-Response Relationship, Drug, Glucagon, Humans, Injections, Subcutaneous, Insulin, Male, Recombinant Proteins, Interleukin-6
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