RSS-Feed abonnieren
DOI: 10.1055/s-0030-1268413
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York
Type 2 Diabetes and Lipoprotein Metabolism Affect LPS-Induced Cytokine and Chemokine Release in Primary Human Monocytes
Publikationsverlauf
received 17.08.2010
first decision 11.10.2010
accepted 25.10.2010
Publikationsdatum:
22. November 2010 (online)
![](https://www.thieme-connect.de/media/eced/201106/lookinside/thumbnails/10.1055-s-0030-1268413-1.jpg)
Abstract
Aims/Hypothesis: Obesity and insulin resistance are characterized by a chronic and low grade state of inflammation and the pro-inflammatory response of monocytes is affected in type 2 diabetes mellitus (T2D). We aimed to investigate whether LPS-induced monocytic cytokine and chemokine release depends on serum lipoprotein parameters in T2D patients.
Methods: Primary human monocytes were isolated from 29 patients with known T2D and from 20 healthy volunteers. Anthropometric and disease-related parameters such as age, gender, BMI, WHR, diabetes duration, diabetes complications, and diabetes control (HbA1c) were documented. Monocytes were stimulated for 18 h with LPS (1 μg/ml). Unstimulated monocytes served as control. The supernatant concentrations of CCL2, CCL3, CCL4, CCL5, MIF and resistin were measured by ELISA.
Results: LPS-stimulation significantly (p<0.001) increased CCL chemokine and resistin concentrations in healthy controls and in patients with T2D, whereas MIF release was not affected in both groups. LPS-induced CCL2 and resistin concentrations were significantly higher in T2D patients when compared to healthy controls. In T2D patients, LPS-induced CCL3 concentration was higher in males when compared to females (p=0.039) and supernatant resistin concentration upon stimulation with LPS showed a significant and positive correlation with age (r=0.6; p=0.001). LPS-induced CCL2 concentration was significantly and positively correlated with serum triglyceride concentration (r=0.4; p=0.009) in T2D patients. Furthermore, LPS-induced CCL4 concentration was significantly and positively correlated with total (r=0.4; p=0.035) and LDL cholesterol (r=0.4; p=0.033) concentration.
Conclusions: LPS responsiveness of monocytes is altered in T2D and is affected by the respective serum lipoprotein metabolism.
Key words
monocyte - LPS - diabetes - chemokine - cytokine - lipoprotein
References
- 1 Weisberg SP, Hunter D, Huber R. et al . CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest. 2006; 116 115-124
- 2 Lehrke M, Lazar MA. Inflamed about obesity. Nat Med. 2004; 10 126-127
- 3 Xu H, Barnes GT, Yang Q. et al . Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003; 112 1821-1830
- 4 Neels JG, Olefsky JM. Inflamed fat: what starts the fire?. J Clin Invest. 2006; 116 33-35
- 5 Schaffler A, Muller-Ladner U, Scholmerich J. et al . Role of adipose tissue as an inflammatory organ in human diseases. Endocr Rev. 2006; 27 449-467
- 6 Wellen KE, Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest. 2003; 112 1785-1788
- 7 Dahlman I, Kaaman M, Olsson T. et al . A unique role of monocyte chemoattractant protein 1 among chemokines in adipose tissue of obese subjects. J Clin Endocrinol Metab. 2005; 90 5834-5840
- 8 Kanda H, Tateya S, Tamori Y. et al . MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest. 2006; 116 1494-1505
- 9 Pataky Z, Bobbioni-Harsch E, Golay A. Obesity: a complex growing challenge. Exp Clin Endocrinol Diabetes. 2010; 118 427-433
- 10 Schlienger JL, Pradignac A, Vinzio S. et al . Hyperglycemia in the critically ill: meaning and treatment. Presse Med. 2009; 38 562-570
- 11 Muller B. Endocrine aspects of critical illness. Ann Endocrinol (Paris). 2007; 68 290-298
- 12 Hickman MS, Schwesinger WH, Page CP. Acute cholecystitis in the diabetic. A case-control study of outcome. Arch Surg. 1988; 123 409-411
- 13 Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005; 115 911-919 quiz 920
- 14 Lue H, Kleemann R, Calandra T. et al . Macrophage migration inhibitory factor (MIF): mechanisms of action and role in disease. Microbes Infect. 2002; 4 449-460
- 15 Kleemann R, Bucala R. Macrophage migration inhibitory factor: critical role in obesity, insulin resistance, and associated comorbidities. Mediators Inflamm. 2010; 610479
- 16 Steppan CM, Lazar MA. The current biology of resistin. J Intern Med. 2004; 255 439-447
- 17 Kopp A, Gross P, Falk W. et al . Fatty acids as metabolic mediators in innate immunity. Eur J Clin Invest. 2009; 39 924-933
- 18 Qatanani M, Szwergold NR, Greaves DR. et al . Macrophage-derived human resistin exacerbates adipose tissue inflammation and insulin resistance in mice. J Clin Invest. 2009;
- 19 Stogbauer F, Neumeier M, Weigert J. et al . Highly efficient and low-cost method to isolate human blood monocytes with high purity. J Immunol Methods. 2008; 337 78-80
- 20 Schmidt-Supprian M, Murphy C, While B. et al . Activated protein C inhibits tumor necrosis factor and macrophage migration inhibitory factor production in monocytes. Eur Cytokine Netw. 2000; 11 407-413
- 21 van der Plas MJ, van Dissel JT, Nibbering PH. Maggot secretions skew monocyte-macrophage differentiation away from a pro-inflammatory to a pro-angiogenic type. PLoS One. 2009; 4 e8071
- 22 Calandra T, Bernhagen J, Mitchell RA. et al . The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. J Exp Med. 1994; 179 1895-1902
- 23 Hsiao HB, Wu JB, Lin H. et al . Kinsenoside Isolated from Anoectochilus Formosanus Suppresses Lipopolysaccharide-Stimulated Inflammatory Reactions in Macrophages and Endotoxin Shock in Mice. Shock July 16, epub ahead of print
- 24 Calandra T. Macrophage migration inhibitory factor and host innate immune responses to microbes. Scand J Infect Dis. 2003; 35 573-576
- 25 Flegel WA, Baumstark MW, Weinstock C. et al . Prevention of endotoxin-induced monokine release by human low- and high-density lipoproteins and by apolipoprotein A-I. Infect Immun. 1993; 61 5140-5146
- 26 Northoff H, Flegel WA, Yurttas R. et al . The role of lipoproteins in the inactivation of endotoxin by serum. Infusionsther Transfusionsmed. 1992a; 19 202-203
- 27 Weinstock C, Ullrich H, Hohe R. et al . Low density lipoproteins inhibit endotoxin activation of monocytes. Arterioscler Thromb. 1992; 12 341-347
- 28 Northoff H, Flegel WA, Yurttas R. et al . The role of lipoproteins in inactivation of endotoxin by serum. Beitr Infusionsther. 1992b; 30 195-197
- 29 Flegel WA, Wolpl A, Mannel DN. et al . Inhibition of endotoxin-induced activation of human monocytes by human lipoproteins. Infect Immun. 1989; 57 2237-2245
- 30 Toso C, Emamaullee JA, Merani S. et al . The role of macrophage migration inhibitory factor on glucose metabolism and diabetes. Diabetologia. 2008; 51 1937-1946
- 31 Akesson L, Gelling RW, Jensen R. et al . Increased lipid oxidation heralds diabetes onset in DR. lyp/lyp rats. Exp Clin Endocrinol Diabetes. 2008; 116 475-480
Correspondence
Prof. Dr. A. SchäfflerMD
Department of Internal
Medicine I
University Medical Center
D–93042 Regensburg
Germany
Telefon: +49/941/944 7009
Fax: +49/941/944 7019
eMail: andreas.schaeffler@klinik.uni-regensburg.de