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Plasma interleukin-6, tumour necrosis factor α and blood cytokine production in type 2 diabetes
Abstract
Type 2 diabetes is associated with increased circulating concentrations of markers of the acute-phase response and interleukin-6 (IL-6). An augmented acute-phase response may be a mechanism which explains many of the clinical and biochemical features of type 2 diabetes and its complications. We sought to confirm that circulating concentrations of the cytokine acute-phase mediators IL-6 and tumour necrosis factor alpha [TNFalpha] are elevated in type 2 diabetes, and investigated blood as a source of cytokines in type 2 diabetes. Blood samples from 20 type 2 diabetic and 17 age-matched healthy subjects were incubated in vitro for 24 hr with and without lipopolysaccharide (LPS) stimulation and secreted cytokines measured. Plasma IL-6 and TNFalpha were significantly increased in type 2 diabetes compared to normal subjects. However, basal production of IL-6 and TNFalpha in cultured diabetic blood was markedly depressed in comparison with non-diabetic samples. IL-6 and TNFalpha production was increased in blood in response to LPS, reaching similar levels in diabetic and non-diabetic subjects, though IL-6 was slightly but significantly higher in controls. We conclude that circulating levels of IL-6 and TNFalpha are increased in type 2 diabetes but there is downregulation of basal cytokine production in blood cells in type 2 diabetes. Blood has the capacity to produce cytokines in diabetes which contribute to the augmented acute-phase response, but the main source of the increased plasma IL-6 and TNFalpha concentrations may be from non-circulating cells.
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In the citing paper
“Interleukin-6 is produced by many cell types including macrophages, adipose cells, and skeletal muscle, and circulating levels are increased in type 2 diabetes (53,54).”
From Expression of Mfn2, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [54]
In the citing paper
“Interleukin-6 is produced by many cell types including macrophages, adipose cells, and skeletal muscle, and circulating levels are increased in type 2 diabetes (53,54).”
From Expression of Mfn2, the Charcot-Marie-Tooth Neuropathy Type 2A Gene, in Human Skeletal Muscle (2005) · cites this paper as [54]
Citations
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Esposito, 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
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529
Inflammation and Activated Innate Immunity in the Pathogenesis of Type 2 Diabetes
Pickup, J. C. (2004) · Diabetes Care · doi:10.2337/diacare.27.3.813 · Cited by 1,414
Self-citationVisser, M., Pahor, M., Taaffe, D. R., Goodpaster, B. H., Simonsick, E. M., Newman, A. B., Nevitt, M., & Harris, T. B. (2002) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/57.5.m326 · Cited by 1,294
IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans
Steensberg, A., Fischer, C. P., Keller, C., Møller, K., & Pedersen, B. K. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00074.2003 · Cited by 1,135
“A number of epidemiological studies have shown increased levels of both TNF- and IL-6 in aging (4), in obese individuals (2), and in patients with type 2 diabetes (13, 17, 24, 34).”
Background
Metadata
- Authors
- Pickup, J. C., Chusney, G. D., Thomas, S. M., & Burt, D.
- Affiliations
- Guy's Hospital (GB)
- Corresponding author
- Pickup, John C.
- Venue
- Life Sciences
- Publisher
- Elsevier BV
- Published
- 2000-06
- Volume
- 67
- Issue
- 3
- Pages
- 291-300
- ISSN
- 0024-3205 (ISSN-L)
- OpenAlex
- W2084483597
- Cited by
- 566
- References
- 0
- Citations by year
- 2026: 4 · 2025: 19 · 2024: 18 · 2023: 21 · 2022: 13 · 2021: 23 · 2020: 26 · 2019: 20 · 2018: 20 · 2017: 17 · 2016: 24 · 2015: 25 · 2014: 35 · 2013: 29 · 2012: 21
- FWCI
- 11.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Life Sciences (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Bupa Foundation
- 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 › Dermatology › Skin Diseases and Diabetes
- Keywords
- type 2 diabetes, interleukin-6, TNF-α, acute phase response, lipopolysaccharide stimulation, plasma cytokines, cytokine downregulation, inflammation in diabetes
- MeSH terms
- Acute-Phase Reaction, Diabetes Mellitus, Type 2, Female, Humans, Immunoenzyme Techniques, Lipopolysaccharides, Male, Middle Aged, Tumor Necrosis Factor-alpha, Interleukin-6, N-Acetylneuraminic Acid
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