Skip to main content
SpringerLink
Log in

The correlation between plasma cytokine levels in jaundice-free children with biliary atresia

  • Original article
  • Published:
World Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Background

T helper (Th) cell cytokines modulate inflammation and play a role in biliary atresia (BA). The aim of the study is a cross-sectional assessment of the levels of Th cytokines in the jaundice-free post Kasai procedure patients.

Methods

There were 40 jaundice-free patients with BA and 28 normal controls enrolled. Patients were divided into 3 groups, including normal liver function, impaired liver function, and portal hypertension. Plasma concentration of Th1 [interferon-γ (INF-γ), interleukin (IL)-2], Th2 (IL-4, IL-10), Th3 [transforming growth factor-β1 (TGF-β1)], Th17 (IL-17) cytokines, and stromal cell-derived factor-1α (SDF-1α) were investigated.

Results

The IFN-γ level was significantly higher in the BA patients with impaired liver function and portal hypertension than controls (P<0.0001 and P<0.0001, respectively). There was a significantly increase of TGF-ß1 in all BA groups compared with controls (P=0.003). The reduction of SDF-1α expression was found in BA groups (P<0.0001). IL-10 levels significantly correlated with aspartate aminotransferase to platelet ratio index (r=0.496, P=0.001). For the cytokine correlations, there were no correlations of Th1, Th2 and Th17 cytokine with the other measured cytokines, but TGF-ß1 was negatively correlated with SDF-1α levels (r=-0.327, P=0.039).

Conclusions

IFN-γ and IL-10 are likely to be involved in the disease progression in BA. Besides, TGF-β1 is found to be a suppression marker associated with SDF-1α levels and reduced production of TGF-β1 may be associated with the disease progression.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Baumann U, Ure B. Biliary atresia. Clin Res Hepatol Gastroenterol 2012;36:257–259.

    Article  PubMed  Google Scholar 

  2. Abdalla AF, Fathy A, Zalata KR, Megahed A, Abo-Alyazeed A, El Regal ME. Morphometric assessment of liver fibrosis may enhance early diagnosis of biliary atresia. World J Pediatr 2013;9:330–335.

    Article  PubMed  Google Scholar 

  3. Mieli-Vergani G, Vergani D. Biliary atresia. Semin Immunopathol 2009;31:371–381.

    Article  PubMed  Google Scholar 

  4. Sun LY, Yang YS, Zhu ZJ, Gao W, Wei L, Sun XY, et al. Outcomes in children with biliary atresia following liver transplantation. Hepatobiliary Pancreat Dis Int 2013;12:143–148.

    Article  PubMed  Google Scholar 

  5. Davenport M, Gonde C, Redkar R, Koukoulis G, Tredger M, Mieli-Vergani G, et al. Immunohistochemistry of the liver and biliary tree in extrahepatic biliary atresia. J Pediatr Surg 2001;36:1017–1025.

    Article  CAS  PubMed  Google Scholar 

  6. Narayanaswamy B, Gonde C, Tredger JM, Hussain M, Vergani D, Davenport M. Serial circulating markers of inflammation in biliary atresia—evolution of the post-operative inflammatory process. Hepatology 2007;46:180–187.

    Article  CAS  PubMed  Google Scholar 

  7. Zheng S, Luo Y, Wang W, Xiao X. Analysis of the pathomorphology of the intra-and extrahepatic biliary system in biliary atresia. Eur J Pediatr Surg 2008;18:98–102.

    Article  CAS  PubMed  Google Scholar 

  8. Mack CL, Tucker RM, Sokol RJ, Karrer FM, Kotzin BL, Whitington PF, et al. Biliary atresia is associated with CD4+ Th1 cell-mediated portal tract infl ammation. Pediatr Res 2004;56:79–87.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Miossec P, Korn T, Kuchroo VK. Interleukin-17 and type 17 helper T cells. N Engl J Med 2009;361:888–898.

    Article  CAS  PubMed  Google Scholar 

  10. Prud’homme GJ, Piccirillo CA. The inhibitory effects of transforming growth factor-beta-1 (TGF-beta1) in autoimmune diseases. J Autoimmun 2000;14:23–42.

    Article  PubMed  Google Scholar 

  11. Dardalhon V, Korn T, Kuchroo VK, Anderson AC. Role of Th1 and Th17 cells in organ-specific autoimmunity. J Autoimmun 2008;31:252–256.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Hammerich L, Heymann F, Tacke F. Role of IL-17 and Th17 cells in liver diseases. Clin Dev Immunol 2011;2011:345803.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Ratajczak MZ, Kim C, Janowska-Wieczorek A, Ratajczak J. The expanding family of bone marrow homing factors for hematopoietic stem cells: stromal derived factor 1 is not the only player in the game. Scientifi cWorldJournal 2012;2012:758512.

  14. Dalakas E, Newsome PN, Harrison DJ, Plevris JN. Hematopoietic stem cell trafficking in liver injury. FASEB J 2005;19:1225–1231.

    Article  CAS  PubMed  Google Scholar 

  15. de Oliveira Fdos S, Kieling CO, dos Santos JL, de Leon Lima PP, Vieira S, Meurer L, et al. Serum and tissue transforming [corrected] growth factor ß1 in children with biliary atresia. J Pediatr Surg 2010;45:1784–1790.

    Article  PubMed  Google Scholar 

  16. Kim SY, Seok JY, Han SJ, Koh H. Assessment of liver fi brosis and cirrhosis by aspartate aminotransferase-to-platelet ratio index in children with biliary atresia. J Pediatr Gastroenterol Nutr 2010;51:198–202.

    Article  CAS  PubMed  Google Scholar 

  17. Wai CT, Greenson JK, Fontana RJ, Kalbfl eisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003;38:518–526.

    Article  PubMed  Google Scholar 

  18. Kobayashi H, Stringer MD. Biliary atresia. Semin Neonatol 2003;8:383–391.

    Article  PubMed  Google Scholar 

  19. Shinkai M, Shinkai T, Puri P, Stringer MD. Elevated expression of IL2 is associated with increased infi ltration of CD8+ T cells in biliary atresia. J Pediatr Surg 2006;41:300–305.

    Article  PubMed  Google Scholar 

  20. Vejchapipat P, Poomsawat S, Chongsrisawat V, Honsawek S, Poovorawan Y. Elevated serum IL-18 and interferon-gamma in medium-term survivors of biliary atresia. Eur J Pediatr Surg 2012;22:29–33.

    Article  CAS  PubMed  Google Scholar 

  21. Wu JF, Chiang BL, Chen HL, Lai HS, Chang MH, Ni YH. Impaired T-lymphocyte proliferation function in biliary atresia patients with chronic cholestatic jaundice after a Kasai operation. Pediatr Res 2006;60:602–606.

    Article  PubMed  Google Scholar 

  22. Couper KN, Blount DG, Riley EM. IL-10: the master regulator of immunity to infection. J Immunol 2008;180:5771–5777.

    Article  CAS  PubMed  Google Scholar 

  23. Meng F, Wang K, Aoyama T, Grivennikov SI, Paik Y, Scholten D, et al. Interleukin-17 signaling in infl ammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology 2012;143:765–776.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Bridoux F, Badou A, Saoudi A, Bernard I, Druet E, Pasquier R, et al. Transforming growth factor beta (TGF-beta)-dependent inhibition of T helper cell 2 (Th2)-induced autoimmunity by self-major histocompatibility complex (MHC) class II-specifi c, regulatory CD4(+) T cell lines. J Exp Med 1997;185:1769–1775.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Kanzler S, Baumann M, Schirmacher P, Dries V, Bayer E, Gerken G, et al. Prediction of progressive liver fibrosis in hepatitis C infection by serum and tissue levels of transforming growth factor-beta. J Viral Hepat 2001;8:430–437.

    Article  CAS  PubMed  Google Scholar 

  26. Vejchapipat P, Theamboonlers A, Poomsawat S, Chittmittrapap S, Poovorawan Y. Serum transforming growth factor-beta1 and epidermal growth factor in biliary atresia. Eur J Pediatr Surg 2008;18:415–418.

    Article  CAS  PubMed  Google Scholar 

  27. Kobayashi H, Horikoshi K, Yamataka A, Lane GJ, Furuhata A, Sueyoshi N, et al. Are stable postoperative biliary atresia patients really stable? Pediatr Surg Int 2001;17:104–107.

    Article  CAS  PubMed  Google Scholar 

  28. Gehling UM, Willems M, Schlagner K, Benndorf RA, Dandri M, Petersen J, et al. Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis. World J Gastroenterol 2010;16:217–224.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Terada R, Yamamoto K, Hakoda T, Shimada N, Okano N, Baba N, et al. Stromal cell-derived factor-1 from biliary epithelial cells recruits CXCR4-positive cells: implications for inflammatory liver diseases. Lab Invest 2003;83:665–672.

    Article  CAS  PubMed  Google Scholar 

  30. Chen CH, Chang LT, Tung WC, Chen YL, Chang CL, Leu S, et al. Levels and values of circulating endothelial progenitor cells, soluble angiogenic factors, and mononuclear cell apoptosis in liver cirrhosis patients. J Biomed Sci 2012;19:66.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Wright N, de Lera TL, García-Moruja C, Lillo R, García-Sánchez F, Caruz A, et al. Transforming growth factor-beta1 down-regulates expression of chemokine stromal cell-derived factor-1: functional consequences in cell migration and adhesion. Blood 2003;102:1978–1984.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Taiwan, China

    Zhi-Hong Jian, Li-Ching Wang, Chieh-Chung Lin & Jiaan-Der Wang

  2. Division of Pediatric Gastroenterology, Department of Pediatrics, Taichung Veterans General Hospital, Taichung City, 40705, Taiwan, China

    Zhi-Hong Jian, Li-Ching Wang, Chieh-Chung Lin & Jiaan-Der Wang

  3. Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung City, 40201, Taiwan, China

    Zhi-Hong Jian

  4. School of Medicine, China Medical University, Taichung, Taiwan, China

    Jiaan-Der Wang

Authors
  1. Zhi-Hong Jian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li-Ching Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chieh-Chung Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiaan-Der Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jiaan-Der Wang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jian, ZH., Wang, LC., Lin, CC. et al. The correlation between plasma cytokine levels in jaundice-free children with biliary atresia. World J Pediatr 11, 352–357 (2015). https://doi.org/10.1007/s12519-015-0023-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12519-015-0023-5

Keywords

Search

Navigation