Relationship Between Serum Concentrations of Interleukin-6 and Tumor Necrosis Factor Alpha in Female Turkish Subjects with Normal and Impaired Glucose Tolerance

Abstract

Serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFα) concentrations were measured in subjects during two-hour glucose loading in order to investigate the effects of glucose on serum IL-6 and TNFα concentrations. Twenty-six female subjects (mean age 60 ± 10 years) had normal glucose tolerance (NGT ) and nineteen female subjects (mean age: 63 ± 9 years) had impaired glucose tolerance (IGT ) according to WHO criteria. Serum IL-6 and TNFα concentrations were measured by chemiluminescent immunometric assay. Subjects with IGT have higher fasting serum TNFα levels than subjects with NGT (p < 0.01). Serum IL-6 and TNFα concentrations were elevated during glucose loading (for each comparision, p < 0.01). The increase in serum TNFα concentrations in IGT was greater than in NGT (p < 0.01). Serum IL-6 and TNFα concentration significantly correlated with insulin and glucose in IGT group (for each comparision, p < 0.01). The correlation between serum glucose and cytokines concentrations was significant in IGT (for each comparision, p < 0.01). There was also a positive correlation between serum IL-6 and TNFα in NGT and IGT (for each comparision, p < 0.01). In conclusion, hyperglycemia is associated with increased circulating cytokine concentrations and fasting TNFα concentrations seem to be more associated with IGT than IL-6.

Key words

Interleukin-6 - tumor necrosis factor-alpha - hyperglycemia - impaired glucose tolerance - cytokines

References

• 1 Caballero A E. Endothelial dysfunction, inflammation, and insulin resistance: a focus on subjects at risk for type 2 diabetes.  Curr Diab Rep. 2004;  4 237-246
• 2 Schmidt M I, Duncan B B, Sharrett A R, Lindberg G, Savage P J, Offenbacher S, Azambuja M I, Tracy R P, Heiss G. Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study.  Lancet. 1999;  353 1649-1652
• 3 Hotamisligil G S, Arner P, Caro J F, Atkinson R L, Spiegelman B M. Increased adipose tissue expression of tumor necrosis factor-in human obesity and insulin resistance.  J Clin Invest. 1995;  95 2409-2415
• 4 Orban Z, Remaley A, Sampson M, Trajanoski Z, Chrousos G P. The differential effect of food intake and beta-adrenergic stimulation on adipose-derived hormones and cytokines in man.   J Clin Endocrinol Metab. 1999;  84 2126-2133
• 5 Fasshauer M, Klein J, Lossner U, Paschke R. Interleukin (IL)-6 mRNA expression is stimulated by insulin, isoproterenol, tumour necrosis factor alpha, growth hormone and IL-6 in 3T3-L1 aipocytes.  Horm Metab Res. 2003;  35 147-152
• 6 Bruun J M, Nielsen C B, Pedersen S B, Flyvbjerg A, Richelsen B. Estrogen reduces pro-imflammatory cytokines in rodent adipose tissue: studies in vivo an in vitro.  Horm Metab Res. 2003;  35 142-146
• 7 Nawawi H, Osman N S, Yusoff K, Khalid B AK. Reduction in serum levels of adhesion molecules, interleukin-6 and C-reactive protein following short-term low-dose atorvastatin treatment in patients with non-familial hypercholesterolemia.  Horm Metab Res. 2003;  35 479-485
• 8 Alberti K G, Zimmet P Z. Definition, Diagnosis and Classification of Diabetes mellitus and its complications. Part 1: Diagnosis and Classification of Diabetes mellitus. Provisional Report of a WHO Consultation.  Diabet Med. 1998;  15 539-553
• 9 Fernandez-Real J M, Ricart W. Insulin resistance and chronic cardiovascular inflammatory syndrom.  Endrocrine Reviews. 2002;  24 278-301
• 10 Harris M I. Impaired glucose tolerance-prevalence and conversion to NIDDM.  Diabet Met. 1996;  13 S9-S11
• 11 Baron A D. Impaired glucose tolerance as a disease.  Am J Cardiol. 2001;  88 16H-19H
• 12 Pickup J C, Chusney G D, Thomas S M, Burt D. Plasma interleukin-6, tumor necrosis factor alpha and blood cytokine production in type 2 diabetes.  Life Sci. 2000;  67 291-300
• 13 Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans. Role of oxidative stress.  Circulation. 2002;  106 2067-2072
• 14 Miyazaki Y, Pipek R, Mandarino L J, De Fronzo R A. Tumor necrosis factor alpha and insulin resistance in obese type 2 diabetic patients.  Int J Obes Relat Metab Disord. 2003;  27 88-94
• 15 Müller S, Martin S, Koenig W, Hanifi-Moghaddam P, Rathmann W, Haastert B, Giani G, Hlig T, Thorand B, Kolb H. Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-α or its receptors.  Diabetologia. 2002;  45 805-812
• 16 Choi K M, Lee J, Lee K W, Seo J A, Oh J H, Kim S G, Kim N H, Choi D S, Baik S H. Comparision of serum concentration of C-reactive protein, TNF-alpha and interleukin 6 between elderly Korean women with normal and impaired glucose tolerance.  Diabetes Res Clin Pract. 2004;  64 99-106
• 17 Bastard J P, Jardel C, Bruckert E, Blondy P, Capeau J, Laville M, Vidal H, Hainque B. Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss.  J Clin Endocrinol Metab. 2000;  85 3338-3342
• 18 Vozarova B, Weyer C, Hanson K, Tataranni P A, Bogardus C, Pratley R E. Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion.  Obesity Res. 2001;  9 414-417
• 19 Mishima Y, Kuyama A, Iada A, Takahashi K, Ishioka I, Kibata M. Relationship between serum tumor necrosis factor-alpha and insulin resistance in obese men with type 2 diabetes mellitus.  Diabetes Res Clin Pract. 2001;  52 119-123
• 20 Lofgren P, van Harmelen V, Reynisdottir S, Naslund E, Ryden M, Rossner S, Arner P. Secretion of Tumor necrosis factor-α shows a strong relationship to insulin-stimulad glucose transport in human adipose tissue.  Diabetes. 2000;  49 688-692
• 21 Blüher M, Kratzsch J, Paschke R. Plasma levels of Tumor necrosis factor alpha, Angiotensin II, Growth Hormone, and IGF-I are not elevated in insulin resistant obese individuals with impaired glucose tolerance.  Diabetes Care. 2001;  24 328-334
• 22 Guha M, Bai W, Nadler J L, Natarajan R. Molecular mechanisms of Tumor necrosis factor alpha gene expression in monocytic cells via hyperglycemia-induced oxidant stress-dependent and independent pathways.  J Biol Chem. 2000;  275 17 728-17 739
• 23 Konukoglu D, Dogan E, Turhan M S, Husrev Hatemi H. Impaired glucose tolerance - is it relevant for early endothelial dysfunction.  Horm Metab Res. 2003;  35 607-610
• 24 Konukoglu D, Hatemi H, Özer E M, Gönen S, Akçay T. The erythrocyte glutathione levels during oral glucose tolerance test.  J Endocrinol Invest. 1997;  20 471-475
• 25 Hatemi H, Yumuk V, Turan N, Arık N. Prevalence of overweight and obesity in Turkey.  Metab Syndr Related Disorders. 2003;  1 285-290