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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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“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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Araújo, L. S., da Silva, M. V., da Silva, C. A., Monteiro, M. L. R., Pereira, L. H. D. M., Rocha, L. P., Corrêa, R. R. M., dos Reis, M. A., & Machado, J. R. (2016) · Journal of Diabetes Mellitus · doi:10.4236/jdm.2016.64025 · Cited by 12
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Jorge, R.-F., Rodrigo, D.-A., Yánez, T. R., Cristina, M.-A. M., Cabrales, J., Ximena, C.-B. M., Amilkar, A.-H., Uparella-Gulfo, I., & Serpa, O. V. V. (2022) · Journal of Biomedical Research & Environmental Sciences · doi:10.37871/jbres1513 · Cited by 11
“Elevated levels of this molecule have been determined in patients with type 2 diabetes mellitus and DKD [24].”
BackgroundSkin Homeostasis and Repair: A T Lymphocyte Perspective
Rhoiney, M., Alvizo, C. R., & Jameson, J. (2023) · The Journal of Immunology · doi:10.4049/jimmunol.2300153 · Cited by 11
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“This response explains many of the clinical and biochemical features of DM2 and its complications [7].”
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“There are an increasing number of studies which suggest that inflammation is one of underlying processes in diabetic nephropathy, associated with up-regulation of various inflammatory parameters (DonateCorrea et al., 2020; Katsuki et al., 1998; Pickup et al., 2000).”
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Continuous positive airway pressure and type 2 diabetes mellitus
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“Inflammatory cytokines, including TNFa and IL-6, elevated in OSA, contribute to insulin resistance [19].”
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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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