Skip to main content

Advertisement

Log in

Pro- and Anti-inflammatory Cytokines in Steatosis and Steatohepatitis

  • Clinical Research
  • Published:
Obesity Surgery Aims and scope Submit manuscript

Abstract

Background

Fatty liver disease is a problem in both bariatric patients and in patients with moderate obesity. Tumor necrosis factor (TNF)-α has been frequently measured in nonalcoholic steatohepatitis (NASH) with or without diabetes, but less is known about interleukin (IL)-6 and IL-10.

Methods

Moderately obese patients (n = 80) with histologically proven steatosis (n = 29) and NASH (n = 51) were recruited. Serum levels of cytokines were documented along with clinical information. The aim was to identify the correlates of such biomolecules in a stable population.

Results

Diabetes tended to be more associated with NASH (52.5% instead of 41.4%, P = 0.015), with no difference of age, gender, or body mass index regarding steatosis. For the entire population, cytokine changes were not significant, including TNF-α and IL-6. In diabetics only, all markers tended to diminish with NASH, especially IL-10 (P = 0.000). IL-10 correlated with homeostatic model assessment index (P = 0.000) and other variables of glucose homeostasis in diabetes, thus representing a major marker of the disease.

Conclusions

(1) Generally inconsistent changes in pro- and anti-inflammatory cytokines occurred when NASH was globally compared to steatosis. (2) In contrast, downregulation of IL-6 and IL-10 was perceived in diabetics with NASH. (3) Arterial hypertension did not play a role in these circumstances. (4) IL-10 maintained strong correlations with glucose metabolism indices. (5) TNF-α could not be incriminated for progressive liver damage, as values failed to increase in NASH. (6) Investigations of IL-10 and other counterregulatory cytokines are lacking in this context and deserve further studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Mummadi RR, Kasturi KS, Chennareddyqari S, et al. Effect of bariatric surgery on nonalcoholic fatty liver disease: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2008;6:1396–402.

    Article  PubMed  Google Scholar 

  2. Mathurin P, Hollebecque A, Arnalsteen L, et al. Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology. 2009;137:532–40.

    Article  CAS  PubMed  Google Scholar 

  3. Dogru T, Ercin CN, Erdem G, et al. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol. 2008;103:3217–8.

    PubMed  Google Scholar 

  4. Wieckowska A, Papouchado B, ZhenZheng L, et al. Increased hepatic and circulating interleukin 6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol. 2008;103:1372–9.

    Article  CAS  PubMed  Google Scholar 

  5. Younossi ZM, Jarrar M, Nugent C, et al. A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis (NASH). Obes Surg. 2008;18:1430–7.

    Article  PubMed  Google Scholar 

  6. Bahcecioglu IH, Yalniz M, Ataseven H, et al. Levels of serum hyaluronic acid, TNF-alpha and IL-8 in patients with nonalcoholic steatohepatitis. Hepatogastroenterology. 2005;52:1549–53.

    CAS  PubMed  Google Scholar 

  7. Gruady SM, Hansen B, Smith Jr SC, et al. Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung and Blood Institute/American Diabetes Association conference on scientific issues related to management. Circulation. 2004;109:551–6.

    Article  Google Scholar 

  8. Kleiner DE, Brunt EM, Natta MV, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–21.

    Article  PubMed  Google Scholar 

  9. Abiru S, Migita K, Maeda Y, et al. Serum cytokine and soluble cytokine receptor levels in patients with non-alcoholic steatohepatitis. Liver Int. 2006;26:39–45.

    Article  CAS  PubMed  Google Scholar 

  10. Naveau S, Balian A, Capron F, et al. Balance between pro and anti-inflammatory cytokines in patients with acute alcoholic hepatitis. Gastroenterol Clin Biol. 2005;29:269–74.

    Article  CAS  PubMed  Google Scholar 

  11. Floreani A, Variola A, Niro G, et al. Plasma adiponectin levels in primary biliary cirrhosis: a novel perspective for link between hypercholesterolemia and atherosclerosis. Am J Gastroenterol. 2008;103:1959–65.

    Article  CAS  PubMed  Google Scholar 

  12. Jarrar MH, Baranova A, Collantes R, et al. Adipokines and cytokines in non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2008;27:412–21.

    Article  CAS  PubMed  Google Scholar 

  13. Isaacs A. Interferon as a factor of recovery from vírus infection. Proc R Soc Med. 1962;55:725–6.

    CAS  PubMed  Google Scholar 

  14. Salgado W, Cunha FQ, Santos JS, et al. Early identification of infectious complications in bariatric surgery by the determination of peritoneal and systemic cytokines. Obes Surg. 2009;19:867–72.

    PubMed  Google Scholar 

  15. Tarantino G, Marra M, Contaldo F, et al. Basal metabolic rate in morbidly obese patients with nonalcoholic fatty liver disease. Clin Invest Med. 2008;31(1):E24–9.

    CAS  PubMed  Google Scholar 

  16. Satapathy SK, Garg S, Chauhan R, et al. Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. Am J Gastroenterol. 2004;99:1946–52.

    Article  CAS  PubMed  Google Scholar 

  17. Lee YM, Sutedja DS, Wai CT, et al. A randomized controlled pilot study of Pentoxifylline in patients with non-alcoholic steatohepatitis (NASH). Hepatol Int. 2008;2:196–201.

    Article  PubMed  Google Scholar 

  18. Kashyap SR, Diab DL, Baker AR, et al. Triglyceride levels and not adipokine concentrations are closely related to severity of nonalcoholic fatty liver disease in an obesity surgery cohort. Obesity (Silver Spring). 2009;17:1696–701.

    Article  CAS  Google Scholar 

  19. Rosenson RS. Treatment of hypertension in metabolic syndrome subjects with amlodipine and olmesartan—effects on oxidized non-esterified free fatty acids and cytokine production. Cardiovasc Drugs Ther. 2009;23:289–94.

    Article  CAS  PubMed  Google Scholar 

  20. Yoneda M, Mawatari H, Fujita K, et al. High-sensitivity C-recative protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and also of severity of fibrosis in NASH. J Gastroenterol. 2007;42:573–82.

    Article  CAS  PubMed  Google Scholar 

  21. Peng XD, Dai LL, Huang CQ, et al. Relationship between anti-fibrotic effect of Panax notoginseng saponins and serum cytokines in rat hepatic fibrosis. Biochem Biophys Res Commun. 2009;388:31–4.

    Article  CAS  PubMed  Google Scholar 

  22. de Lalla C, Galli G, Aldrighetti L. Production of profibrotic cytokines by invariant NKT cells characterizes cirrhosis progression in chronic viral hepatitis. J Immunol. 2004;173:1417–25.

    PubMed  Google Scholar 

  23. Hong EG, Ko HJ, Cho YR, et al. Interleukin-10 prevents diet-induced insulin resistance by attenuating macrophage and cytokine response in skeletal muscle. Diabetes. 2009;58:2525–35.

    Article  CAS  PubMed  Google Scholar 

  24. Elinav E, Pappo O, Sklair-Levy M, et al. Amelioration of non-alcogholic steatohepatitis and glucose intolerance in ob/ob mice by oral immune regulation towards liver-extracted proteins is associated with elevated intrahepatic NKT lymphocytes and serum IL-10 levels. J Pathol. 2006;208:74–81.

    Article  CAS  PubMed  Google Scholar 

  25. Estep JM, Baranova A, Hossain N, et al. Expression of cytokine signaling genes in morbidly obese patients with non-alcoholic steatohepatitis and hepatic fibrosis. Obes Surg. 2009;19:617–24.

    Article  PubMed  Google Scholar 

  26. Yamaguchi K, Yang L, McCall S, et al. Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology. 2007;45:1366–74.

    Article  CAS  PubMed  Google Scholar 

  27. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214:199–210.

    Article  CAS  PubMed  Google Scholar 

  28. Park EJ, Lee JH, Yu GY, et al. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell. 2010;140:197–208.

    Article  CAS  PubMed  Google Scholar 

  29. Chagas AL, Kikuchi LO, Oliveira CP, et al. Does hepatocellular carcinoma in nonalcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients? Braz J Med Biol Res. 2009;42:958–62.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest statement

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Claudia P. M. S. Oliveira.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rabelo, F., Oliveira, C.P.M.S., Faintuch, J. et al. Pro- and Anti-inflammatory Cytokines in Steatosis and Steatohepatitis. OBES SURG 20, 906–912 (2010). https://doi.org/10.1007/s11695-010-0181-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11695-010-0181-4

Keywords

Navigation