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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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BackgroundMicroarray profiling of gene expression in human adipocytes in response to anthocyanins
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“There is growing evidence that chronic inflammation has a role in the pathogenesis of type 2 diabetes (Pickup et al. 2000, Marette 2002), but it has been shown that nitric oxide (NO) has a regulatory effect in the immune system (van der Veen 2001).”
BackgroundInfluentialThe linkage between inflammation and Type 2 diabetes mellitus
Cruz, N., Sousa, L. P., Sousa, M. O., Pietrani, N. T., Fernandes, A. P., & Gomes, K. B. (2012) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2012.09.003 · Cited by 161
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Proinflammatory Cytokines, Insulin Resistance, and Insulin Secretion in Chronic Hepatitis C patients
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Glucose Enhances Human Macrophage LOX-1 Expression
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Hamid, Y. H., Rose, C. S., Urhammer, S. A., Gl�mer, C., Nols�e, R., Kristiansen, O. P., Mandrup-Poulsen, T. R., Borch‐Johnsen, K., Jørgensen, T., Hansen, T. F., et al. (2005) · Diabetologia · doi:10.1007/s00125-004-1623-0 · Cited by 157
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Interleukin‐6 production in human subcutaneous abdominal adipose tissue: the effect of exercise
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“A higher level of IL-6 in plasma is seen in type 2 diabetes mellitus patients (Bastard et al. 2000; Pickup et al. 2000).”
Background12/15‐Lipoxygenase Products Induce Inflammation and Impair Insulin Signaling in 3T3‐L1 Adipocytes
Chakrabarti, S. K., Cole, B. K., Wen, Y., Keller, S. R., & Nadler, J. L. (2009) · Obesity · doi:10.1038/oby.2009.192 · Cited by 153
Adipocytokines Attenuate the Association Between Visceral Adiposity and Diabetes in Older Adults
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Nassar, H. A., Kantarcı, A., & Dyke, T. E. V. (2007) · Periodontology 2000 · doi:10.1111/j.1600-0757.2006.00168.x · Cited by 151
“activation of innate immunity are involved in the pathogenesis of the disease’s complications (85, 86).”
BackgroundPeriodontitis and type II diabetes: a two-way relationship
Chee, B., Park, B., & Bartold, P. M. (2013) · International Journal of Evidence-Based Healthcare · doi:10.1111/1744-1609.12038 · Cited by 155
Dinh, W., Füth, R., Nickl, W., Krahn, T., Ellinghaus, P., Scheffold, T., Bansemir, L., Bufe, A., Barroso, M. C., & Lankisch, M. (2009) · Cardiovascular Diabetology · doi:10.1186/1475-2840-8-58 · Cited by 149
Potential Role of Serum and Urinary Biomarkers in Diagnosis and Prognosis of Diabetic Nephropathy
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“Elevated serum levels of IL-6 have been associated with the progression of DN in type 2 diabetic patients.(112,177) Sekizuka et al first reported that levels of IL-6 were significantly higher in the serum of type 2 diabetic patients with nephropathy compared with diabetic patients without nephropathy.”
BackgroundPark, C., Hsu, C.-H., Neelakanta, G., Nourmand, H., Braunfeld, M. Y. C., Wray, C. L., Steadman, R. H., Hu, K., Cheng, R. T., & Xia, V. W. (2009) · Transplantation · doi:10.1097/tp.0b013e31819cc3e6 · Cited by 146
“Proinflammatory cytokines, such as tumor necrosis factor- , interleukin-1 , and -18 are significantly increased by hyperglycemia, whereas these cytokines are suppressed by insulin (30, 34).”
BackgroundPreeclampsia and the systemic inflammatory response
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Intrauterine growth restriction and adult disease: the role of adipocytokines
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p38 Mitogen-activated Protein Kinase Plays a Stimulatory Role in Hepatic Gluconeogenesis
Cao, W., Collins, Q. F., Becker, T. C., Robidoux, J., Lupo, E. G., Xiong, Y., Daniel, K. W., Floering, L. M., & Collins, S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506223200 · Cited by 145
High resistin and interleukin-6 levels are associated with gestational diabetes mellitus
Kuźmicki, M., Telejko, B., Szamatowicz, J., Zonenberg, A., Nikołajuk, A., Kretowski, A. J., & Górska, M. (2009) · Gynecological Endocrinology · doi:10.1080/09513590802653825 · Cited by 145
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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