Abstract
Tumor necrosis factor (TNF-α) is a cytokine involved in systemic inflammation during acute phase reactions. The current study was designed to investigate the levels of pro-inflammatory cytokine (TNF-α) along with the anti-inflammatory cytokine (IL-10) during progression of non-alcoholic fatty liver disease (NAFLD) from simple steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis in diabetic patients, and correlate the levels of cytokines with the progression of NAFLD. Fifty-two diabetic patients compared to 18 healthy controls were participated in this study. Based on clinical diagnosis, patients were divided into three groups: simple steatosis, NASH and fibrosis. Serum liver function tests, fasting blood glucose, bilirubin, ALT, AST, TNF-α, IL-10 and lipid profile were measured. TNF-α levels were significantly higher in NAFLD patients compared to control subjects with a significant positive correlation with body mass index and fasting blood glucose (FBG) but with negative correlation with IL-10. Serum IL-10 levels were significantly lower in NAFLD patients compared with controls. A positive correlation between IL-10 and HDL-C with concomitant negative correlation between IL-10 and FBG and triacylglycerides was found. Cytokine analyses showed that there was a prominent imbalance between TNF-α and IL-10 in patients with NAFLD, and this imbalance increase by increasing the progression of NAFLD especially in obese diabetic patients. TNF-α and IL-10 could be used in diagnosis and follow-up of NAFLD stages in a way to avoid liver biopsies in greater proportion of patients.
Similar content being viewed by others
References
Zelber-Sagi S, Lotan R, Shlomai A, Webb M, Harrari G, Buch A, et al. Predictors for incidence and remission of NAFLD in the general population during a seven-year prospective follow-up. J Hepatol. 2012;56:1145–51.
Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003;37(4):917–23.
Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology. 2012;142(4):711–25.
Charlton M. Nonalcoholic fatty liver disease: a review of current understanding and future impact. Clin Gastroenterol Hepatol. 2004;2:1048–58.
Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology. 1998;114:842–5.
Albano E. Oxidative mechanisms in the pathogenesis of alcoholic liver disease. Mol Aspects Med. 2008;29:9–16.
Koek GH, Liedorp PR, Bast A. The role of oxidative stress in non-alcoholic steatohepatitis. Clin Chim Acta. 2011;412:1297–305.
Wong VW, Chan HL, Hui AY, Chan KF, Liew CT, Chan FK, Sung JJ. Clinical and histological features of non-alcoholic fatty liver disease in Hong Kong Chinese. Aliment Pharmacol Ther. 2004;20(1):45–9.
Angulo P. Non alcoholic fatty liver disease. N Engl J Med. 2002;346:1221–31.
Vanni E, Bugianesia E, Kotronen A, De Minicis S, Yki-Järvinen H, Svegliati-Baroni G. From the metabolic syndrome to NAFLD or vice versa? Dig Liver Dis. 2010;42:320–30.
Rolo AP, Teodoro JS, Palmeira CM. Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radic Biol Med. 2012;52:59–69.
Crews FT, Bechara R, Brown LA, Guidot DM, Mandrekar P, Oak S, Qin L, Szabo G, Wheeler M, Zou J. Cytokines and alcohol. Alcohol Clin Exp Res. 2006;30:720–30.
Cameron RG, Neuman MG. Novel morphologic findings in alcoholic liver disease. Clin Biochem. 1999;32(7):579–84.
Das SK, Balakrishnan V. Role of cytokines in the pathogenesis of non-alcoholic fatty liver disease. Ind J Clin Biochem. 2011;26(2):202–9.
Tilg H. The role of cytokines in non-alcoholic fatty liver disease. Dig Dis. 2010;28(1):179–85.
Mottin CC, Moretto M, Padoin AV. The role of ultrasound in the diagnosis of hepatic steatosis in morbidly obese patients. Obes Surg. 2004;14:635–7.
Freidewald WT, Levy RJ, Fredrickson DS. Estimation of concentration of low density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499–502.
Stepaniak J, Shuster J, Sundick R. Production and determination of recombinant human cytokines. J Cytokine Res. 1995;19:515–26.
Carter-Kent C, Zein NN, Feldstein AE. Cytokines in the pathogenesis of fatty liver and disease progression to steatohepatitis: implications for treatment cytokines in NAFLD. Am J Gastroenterol. 2008;103:1036–42.
Lu H, Zeng L, Liang B, Shu X, Xie D. High prevalence of coronary heart disease in type 2 diabetic patients with non-alcoholic fatty liver disease. Arch Med Res. 2009;40:571–5.
Edens M, Kuipers F, Stolk R. Non-alcoholic fatty liver disease is associated with cardiovascular disease risk markers. Obes Rev. 2009;10:412–9.
Collier J. Non-alcoholic fatty liver disease. Medicine. 2007;35(2):86–8.
Giorgio R, Wolfgang K, Joseph S, Klaus P. Non-alcoholic fatty liver disease in obese children evaluated by magnetic resonance imaging. Acta Pediatr. 2006;95(7):833–7.
Steve C, Anna M. Role of inflammation in nonalcoholic steatohepatitis. Curr Opin Gastroenterol. 2005;21(6):702–7.
Riley TR, Taheri M, Schreibman IR. Does weight history affect fibrosis in the setting of chronic liver disease? J Gastrointest Liver Dis. 2009;18(3):299–302.
Bugianesi E, Zannoni C, Vanni E, Marzocchi R, Marchesini G. Non-alcoholic fatty liver and insulin resistance: a cause–effect relationship? Dig Liver Dis. 2004;36(3):165–73.
Uchil D, Pipalia D, Chawla M, Patel R, Maniar S, Narayani, Juneja A. Non-alcoholic fatty liver disease (NAFLD)—The hepatic component of metabolic syndrome. J Assoc Physicians India. 2009;57:201–4.
Simonen P, Kotronen A, Hallikainen M, Sevastianova K, Makkonen J, Hakkarainen A, et al. Cholesterol synthesis is increased and absorption decreased in non-alcoholic fatty liver disease independent of obesity. J Hepatol. 2011;54:153–9.
Nobili V, Alisi A, Vania A, Tiribelli C, Pietrobattista A, Bedogni G. The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease. BMC Med. 2009;7(21).
Mouralidarane A, Oben JA, Soeda J. Pathophysiology and clinical management of nonalcoholic fatty liver disease. Medicine. 2011;39(10):592–6.
Peraldi P, Hotamisligil GS, Buurman WA, White MF, Spiegelman BM. Tumor necrosis factor (TNF)-alpha inhibits insulin signaling through stimulation of the p55 TNF receptor and activation of sphingomyelinase. J Biol Chem. 1996;271(22):13018–22.
Tilg H, Diehl AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med. 2000;343:1467–76.
Wei Y, Rector RS, Thyfault JP, Ibdah JA. Nonalcoholic fatty liver disease and mitochondrial dysfunction. World J Gastroenterol. 2008;14(2):193–9.
Zhang L, Wang XZ. Interleukin-10 and chronic liver disease. World J Gastroenterol. 2006;12(11):1681–5.
Straczkowski M, Kowalska I, Nikolajuk A, Krukowska A, Gorska M. Plasma interleukin-10 concentration is positively related to insulin sensitivity in young healthy individuals. Diabetes Care. 2005;28(8):2036–7.
Uysal S, Armutcu F, Aydogan T, Akin K, Ikizek M, Yigitoglu MR. Some inflammatory cytokine levels, iron metabolism and oxidan stress markers in subjects with nonalcoholic steatohepatitis. Clin Biochem. 2011;44(17–18):1375–9.
Angulo P. Treatment of non alcoholic fatty liver disease. Ann Hepatol. 2002;1(1):12–9.
Cintra DE, Pauli JR, Araújo EP, Moraes JC, De Souza CT, Milanski M, et al. Interleukin-10 is a protective factor against diet-induced insulin resistance in liver. J Hepatol. 2008;48(4):628–37.
Braunersreuther V, Viviani GL, Mach F, Montecucco F. Role of cytokines and chemokines in non-alcoholic fatty liver disease. World J Gastroenterol. 2012;18(8):727–35.
Hashem RM, Mahmoud MF, El-Moselhy MA, Soliman HM. Interleukin-10 to tumor necrosis factor-alpha ratio is a predictive biomarker in nonalcoholic fatty liver disease: interleukin-10 to tumor necrosis factor-alpha ratio in steatohepatitis. Eur J Gastroenterol Hepatol. 2008;20(10):995–1001.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zahran, W.E., Salah El-Dien, K.A., Kamel, P.G. et al. Efficacy of Tumor Necrosis Factor and Interleukin-10 Analysis in the Follow-up of Nonalcoholic Fatty Liver Disease Progression. Ind J Clin Biochem 28, 141–146 (2013). https://doi.org/10.1007/s12291-012-0236-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12291-012-0236-5