Increased serum concentrations of inflammatory cytokines in type 2 diabetic patients with chronic kidney disease


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Abstract

Aim. To study the relationship between serum inflammatory cytokine levels in chronic kidney disease patients with type 2 diabetes. Subjects and methods. Sixty-four patients aged 43 to 70 years with a glomerular filtration rate (GFR) of >30 ml/min/1.73 m2 were examined. A control group consisted of 15 healthy individuals. The serum concentration of macrophage colony-stimulating factor (M-CSF), macrophage inflammatory protein 1α (MIP-1α), macrophage migration inhibitory factor (MIF), interleukin 6 (IL-6), as well as the urinary excretion of albumin and type IV collagen was determined by enzyme immunoassay. Results. In patients with a GFR of >60 ml/min/1.73 m2, M-CSF and MIF concentrations proved to be significantly higher than those in the control group (p=0.0003 and p=0.001, respectively). In those with a GFR of 30-59 ml/min/1.73 m2, there was an increase in the levels of M-CSF (p<0.0001), MIP-1α (p=0.002), MIF (p=0.02), and IL-6 (p=0.02). The decline in GFR was associated with the higher levels of M-CSF (p=0.02) and MIP-1α (p=0.02) and with the higher urinary excretion of type IV collagen (p=0.01). M-CSF, MIP-1α, and IL-6 correlated positively with the urinary excretion of albumin (r=0.34, r=0.28, and r=0.28, respectively; all p<0.05) and type IV collagen (r=0.31, r=0.4, and r=0.43, respectively; all p<0.05). Conclusion. The findings confirm the concept that chronic inflammation is involved in the development of diabetic kidney disease.

References

  1. Wada J, Makino H. Inflammation and the pathogenesis of diabetic nephropathy. Clin Sci (Lond). 2013;124(3):139-152.
  2. Бондарь И.А., Климонтов В.В. Иммуновоспалительные механизмы в формировании диабетической нефропатии. Проблемы эндокринологии. 2007;2:34-40.
  3. Chow F, Ozols E, Nikolic-Paterson DJ, Atkins RC, Tesch GH. Macrophages in mouse type 2 diabetic nephropathy: Correlation with diabetic state and progressive renal injury. Kidney Int. 2004;65(1):116-128.
  4. Nguyen D, Ping F, Mu W, Hill P, Atkins RC, Chadban SJ. Macrophage accumulation in human progressive diabetic nephropathy. Nephrology (Carlton). 2006;11(3):226-231.
  5. Бондарь И.А., Климонтов В.В., Надeев А.П. Мочевая экскреция провоспалительных цитокинов и трансформирующего фактора роста β на ранних стадиях диабетической нефропатии. Терапевтический архив. 2008;1:52-56.
  6. Nagase R, Kajitani N, Shikata K, Ogawa D, Kodera R, Okada S, Kido Y, Makino H. Phenotypic change of macrophages in the progression of diabetic nephropathy; sialoadhesin-positive activated macrophages are increased in diabetic kidney. Clin Exp Nephrol. 2012;16(5):739-748.
  7. Seok SJ, Lee ES, Kim GT, Hyun M, Lee JH, Chen S, Choi R, Kim HM, Lee EY, Chung CH. Blockade of CCL2/CCR2 signalling ameliorates diabetic nephropathy in db/db mice. Nephrol Dial Transplant. 2013;28(7):1700-1710.
  8. You H, Gao T, Cooper TK, Brian Reeves W, Awad AS. Macrophages directly mediate diabetic renal injury. Am J Physiol Renal Physiol. 2013;305(12):F1719-F1727.
  9. Lv SS, Liu G, Wang JP, Wang WW, Cheng J, Sun AL, Liu HY, Nie HB, Su MR, Guan GJ. Mesenchymal stem cells transplantation ameliorates glomerular injury in streptozotocin-induced diabetic nephropathy in rats via inhibiting macrophage infiltration. Int Immunopharmacol. 2013;17(2):275-282.
  10. Hellemons ME, Kerschbaum J, Bakker SJ, Neuwirt H, Mayer B, Mayer G, de Zeeuw D, Lambers Heerspink HJ, Rudnicki M. Validity of biomarkers predicting onset or progression of nephropathy in patients with Type 2 diabetes: a systematic review. Diabet Med. 2012;29(5):567-577.
  11. Шамхалова М.Ш., Курумова К.О., Клефортова И.И., Ситкин И.И., Ильин А.В., Арбузова М.И., Гончаров Н.П., Кация Г.В., Александров А.А., Кухаренко С.С., Шестакова М.В., Дедов И.И. Факторы развития туболоинтерстициального повреждения почек у больных сахарным диабетом. Сахарный диабет. 2010;3:134-141.
  12. Lan HY, Yang N, Nikolic-Paterson DJ, Yu XQ, Mu W, Isbel NM, Metz CN, Bucala R, Atkins RC. Expression of macrophage migration inhibitory factor in human glomerulonephritis. Kidney Int. 2000;57:499-509.
  13. Isbel NM, Nikolic-Paterson DJ, Hill PA, Dowling J, Atkins RC. Local macrophage proliferation correlates with increased renal M-CSF expression in human glomerulonephritis. Nephrol Dial Transplant. 2001;16(8):1638-1647.
  14. Herder C, Kolb H, Koenig W, Haastert B, Müller-Scholze S, Rathmann W, Holle R, Thorand B, Wichmann HE. Association of systemic concentrations of macrophage migration inhibitory factor with impaired glucose tolerance and type 2 diabetes: Results from the Cooperative Health Research in the Region of Augsburg, Survey 4 (KORA S4). Diabetes Care. 2006;29:368-371.
  15. Vozarova B, Stefan N, Hanson R, Lindsay RS, Bogardus C, Tataranni PA, Metz C, Bucala R. Plasma concentrations of macrophage migration inhibitory factor are elevated in Pima Indians compared to Caucasians and are associated with insulin resistance. Diabetologia. 2002;45:1739-1741.
  16. Yu XY, Chen HM, Liang JL, Lin QX, Tan HH, Fu YH, Liu XY, Shan ZX, Li XH, Yang HZ, Yang M, Li Y, Lin SG. Hyperglycemic myocardial damage is mediated by proinflammatory cytokine: macrophage migration inhibitory factor. PLoS One. 2011; 6(1):e16239.
  17. Chatzigeorgiou A, Harokopos V, Mylona-Karagianni C, Tsouvalas E, Aidinis V, Kamper EF. The pattern of inflammatory/anti-inflammatory cytokines and chemokines in type 1 diabetic patients over time. Ann Med. 2010;42(6):426-438.
  18. Watanabe T, Tomioka NH, Doshi M, Watanabe S, Tsuchiya M, Hosoyamada M. Macrophage migration inhibitory factor is a possible candidate for the induction of microalbuminuria in diabetic db/db mice. Biol Pharm Bull. 2013;36(5):741-747.
  19. Liu J, Zhao Z, Willcox MD, Xu B, Shi B. Multiplex bead analysis of urinary cytokines of type 2 diabetic patients with normo- and microalbuminuria. J Immunoassay Immunochem. 2010;31(4):279-289.
  20. Sanchez-Niño MD, Sanz AB, Ihalmo P, Lassila M, Holthofer H, Mezzano S, Aros C, Groop PH, Saleem MA, Mathieson PW, Langham R, Kretzler M, Nair V, Lemley KV, Nelson RG, Mervaala E, Mattinzoli D, Rastaldi MP, Ruiz-Ortega M, Martin-Ventura JL, Egido J, Ortiz A. The MIF receptor CD74 in diabetic podocyte injury. J Am Soc Nephrol. 2009;20(2):353-362.
  21. Wang Z, Wei M, Wang M, Chen L, Liu H, Ren Y, Shi K, Jiang H. Inhibition of macrophage migration inhibitory factor reduces diabetic nephropathy in type II diabetes mice. Inflammation. 2014;37(6):2020-2029. doi: 10.1007/s10753-014-9934-x.
  22. Leung JC, Chan LY, Tsang AW, Liu EW, Lam MF, Tang SC, Lai KN. Anti-macrophage migration inhibitory factor reduces transforming growth factor-beta 1 expression in experimental IgA nephropathy. Nephrol Dial Transplant. 2004;19(8):1976-1985.
  23. Lim AK, Ma FY, Nikolic-Paterson DJ, Thomas MC, Hurst LA, Tesch GH. Antibody blockade of c-fms suppresses the progression of inflammation and injury in early diabetic nephropathy in obese db/db mice. Diabetologia. 2009;52(8):1669-1679. doi: 10.1007/s00125-009-1399-3.
  24. Qi W, Chen X, Zhang Y, Holian J, Mreich E, Gilbert RE, Kelly DJ, Pollock CA. High glucose induces macrophage inflammatory protein-3 alpha in renal proximal tubule cells via a transforming growth factor-beta 1 dependent mechanism. Nephrol Dial Transplant. 2007;22(11):3147-3153.
  25. Cherney DZ, Scholey JW, Sochett E, Bradleу TJ, Reich HN. The acute effect of clamped hyperglycemia on the urinary excretion of inflammatory cytokines/chemokines in uncomplicated type 1 diabetes: a pilot study. Diabetes Care. 2011;34(1):177-180. doi: 10.2337/dc10-1219.
  26. Ghanim H, Korzeniewski K, Sia CL, Chang Ling Sia, Sanaa Abuaysheh, Teekam Lohano, Ajay Chaudhuri, Paresh Dandona. Suppressive effect of insulin infusion on chemokines and chemokine receptors. Diabetes Care. 2010;33(5):1103-1108. doi: 10.2337/dc09-2193.
  27. Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm. 2013;2013:139239.
  28. Levine JA, Jensen MD, Eberhardt NL, O’Brien T. Adipocyte macrophage colony-stimulating factor is a mediator of adipose tissue growth. J Clin Invest. 1998;101(8):1557-1564.
  29. Skurk T, Herder C, Kräft I, Müller-Scholze S, Hauner H, Kolb H. Production and release of macrophage migration inhibitory factor from human adipocytes. Endocrinology. 2005;146(3):1006-1011.
  30. Fain J.N. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm. 2006;74:443-477.
  31. Ndisang JF, Jadhav A, Mishra M. The heme oxygenase system suppresses perirenal visceral adiposity, abates renal inflammation and ameliorates diabetic nephropathy in Zucker diabetic fatty rats. PLoS One. 2014;9(1):e87936.
  32. Коненков В.И., Шевченко А.В., Прокофьев В.Ф. Фазуллина О.Н. Ассоциации вариантов гена фактора роста сосудистого эндотелия (VEGF) и генов цитокинов (IL-1В, IL-4, IL-6, IL-10, TNFA) c сахарным диабетом 2-го типа у женщин. Сахарный диабет. 2012;3:4-10.
  33. Ng DP, Nurbaya S, Ye SH, Krolewski AS. An IL-6 haplotype on human chromosome 7p21 confers risk for impaired renal function in type 2 diabetic patients. Kidney Int. 2008;74(4):521-527.
  34. Papaoikonomou S, Tentolouris N, Tousoulis D, Papadodiannis D, Miliou A, Papageorgiou N, Hatzis G, Stefanadis C. The association of the 174G>C polymorphism of interleukin 6 gene with diabetic nephropathy in patients with type 2 diabetes mellitus. J Diabetes Complications. 2013;27(6):576-579. doi: 10.1016/j.jdiacomp.2013.06.006.
  35. Fernández Fernández B, Elewa U, Sánchez-Niño MD, Rojas-Rivera JE, Martin-Cleary C, Egido J, Ortiz A. 2012 update on diabetic kidney disease: the expanding spectrum, novel pathogenic insights and recent clinical trials. Minerva Med. 2012;103(4): 219-234.

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