The DOI matches its Crossref record.
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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“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]
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Patrizi, R. M. (2008) · University Microfilms International eBooks · Cited by 1
(2015) · Inflammation and Cell Signaling · doi:10.14800/ics.926 · Cited by 1
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Shahida, R., Farasat, T., Naz, S., et al. (2017) · Pakistan Journal of Zoology · doi:10.17582/journal.pjz/2017.49.6.2153.2159 · Cited by 1
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Wang, L. (2007) · UKnowledge (University of Kentucky)
Konenkov, V. I., Shevchenko, A. V., Korolev, M. A., et al. (2010) · Osteoporosis and Bone Diseases · doi:10.14341/osteo201035-12
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BackgroundBowen, M. J. (2015) · University Library - University of Saskatchewan (University of Saskatchewan)
Renke, M. (2009)
The Scientific Analysis on Exercise and Endotoxin.
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Yang, L., Li, M., Cui, X., et al. (2016) · doi:10.2991/bbe-16.2016.54
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Santaren, I. D. (2014) · TSpace (University of Toronto)
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Urbina, P. (2013) · Journal of International Crisis and Risk Communication Research
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BackgroundKarimzad, S. (2018) · Aston Publications Explorer (Aston University) · doi:10.48780/publications.aston.ac.uk.00037698
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Na, W., Yu, T. Y., & Sohn, C. (2023) · Nutrition Research and Practice · doi:10.4162/nrp.2023.17.3.529
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BackgroundMeur, G., Anindya, R., & Rutter, G. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13195-0.00010-7 · Cited by 2
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Yen, C., Lo, C., Lee, J., Liu, K., Li, C., Lii, C., Hsu, C.-E., Yang, Y., & Chen, H. (2025) · Antioxidants · doi:10.3390/antiox14101155
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Naicker, Y., & Khathi, A. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47110884
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Wang, P.-H., Ho, C., Liao, K., et al. (2025) · Journal of Infection and Public Health · doi:10.1016/j.jiph.2025.103089
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Pires, J. R. (2008) · Americanae (AECID Library)
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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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