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Serum interleukin-8 in children with biliary atresia: relationship with disease stage and biochemical parameters

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Abstract

Biliary atresia (BA) is a neonatal obliterative cholangiopathy of unknown etiology. Despite the Kasai procedure, hepatic fibrosis and portal hypertension (PH) still occur. Interleukin-8 (IL-8) is an important mediator of inflammation and immune response in human disease. The objective of this study was to investigate the potential role of IL-8 in the pathogenesis of the progressive, sclerosing, inflammatory process and fibrosis in BA. A total of 60 pediatric patients with BA and 15 healthy children were evaluated. The mean ages of BA patients and controls were 6.3±0.6 and 6.7±1.1 years, respectively. The patients were classified into two groups according to their clinical outcomes: patients with jaundice (total bilirubin ±25.5 μmol/l) and patients without jaundice (total bilirubin <25.5 μmol/l). The IL-8 levels in serum samples were determined by commercially available enzyme-linked immunosorbent assay. Serum IL-8 levels were higher in the BA patients than in healthy children (236.2±60.1 vs. 34.5±12.1 pg/ml, P<0.001). Patients with jaundice had lower levels of albumin but had greater levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transpeptidase compared with patients without jaundice. Serum IL-8 levels in the jaundice group were significantly higher than in those without jaundice (516.5±130.0 vs. 49.3±10.4 pg/ml, P<0.0005). Furthermore, patients with PH had higher IL-8 levels than those without PH (378.1±102.2 vs. 106.6±48.4 pg/ml, P<0.005). In the jaundice-free group, IL-8 levels were elevated in patients with PH compared with those without PH (79.0±17.4 vs. 19.7±5.8 pg/ml, P<0.005). The present study demonstrated elevation of serum IL-8 levels in children with BA. Serum IL-8 levels were also higher in patients with jaundice compared with patients without jaundice. These findings suggest that IL-8 may play a significant role in the pathogenesis of BA.

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References

  1. Balistreri WF, Grand R, Hoofnagle JH, Suchy FJ, Ryckman FC, Perlmutter DH, Sokol RJ (1996) Biliary atresia: current concepts and research directions. Summary of a symposium. Hepatology 23:1682–1692

    Google Scholar 

  2. Alagille D (1984) Extrahepatic biliary atresia. Hepatology 4:7S–10S

    Google Scholar 

  3. Karrer FM, Price MR, Bensard DD, Sokol RJ, Narkewicz MR, Smith DJ, Lilly JR (1996) Long-term results with the Kasai operation for biliary atresia. Arch Surg 131:493–496

    Google Scholar 

  4. Chuang JH, Lin JN (2001) Biliary atresia at the dawn of a new century. Chang Gung Med J 24:217–228

    Google Scholar 

  5. Tilg H, Wilmer A, Vogel W, Herold M, Nolchen B, Judmaier G, Huber C (1992) Serum levels of cytokines in chronic liver diseases. Gastroenterology 103:264–274

    Google Scholar 

  6. Kobayashi H, Narumi S, Tamatani T, Lane GJ, Miyano T (1999) Serum IFN-inducible protein-10: a new clinical prognostic predictor of hepatocyte death in biliary atresia. J Pediatr Surg 34:308–311

    Google Scholar 

  7. Tamatani T, Kobayashi H, Tezuka K, Sakamoto S, Suzuki K, Nakanishi T, Takigawa M, Miyano T (1998) Establishment of the enzyme-linked immunosorbent assay for connective tissue growth factor (CTGF) and its detection in the sera of biliary atresia. Biochem Biophys Res Commun 251:748–752

    Article  CAS  PubMed  Google Scholar 

  8. Miller MD, Krangel MS (1992) Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines. Crit Rev Immunol 12:17–46

    Google Scholar 

  9. Schroder JM (1989) The monocyte-derived neutrophil activating peptide (NAP/interleukin 8) stimulates human neutrophil arachidonate-5-lipoxygenase, but not the release of cellular arachidonate. J Exp Med 170:847–863

    Google Scholar 

  10. Nakamura H, Yoshimura K, McElvaney NG, Crystal RG (1992) Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line. J Clin Invest 89:1478–1484

    Google Scholar 

  11. Donnelly SC, Strieter RM, Kunkel SL, Walz A, Robertson CR, Carter DC, Grant IS, Pollok AJ, Haslett C (1993) Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet 341:643–647

    Article  CAS  PubMed  Google Scholar 

  12. Marini M, Vittori E, Hollemborg J, Mattoli S (1992) Expression of the potent inflammatory cytokines, granulocyte-macrophage-colony-stimulating factor and interleukin-6 and interleukin-8, in bronchial epithelial cells of patients with asthma. J Allergy Clin Immunol 89:1001–1009

    Google Scholar 

  13. Huang YS, Chan CY, Wu JC, Pai CH, Chao Y, Lee SD (1996) Serum levels of interleukin-8 in alcoholic liver disease: relationship with disease stage, biochemical parameters and survival. J Hepatol 24:377–384

    Google Scholar 

  14. Masumoto T, Ohkubo K, Yamamoto K, Ninomiya T, Abe M, Akbar SM, Michitaka K, Horiike N, Onji M (1998) Serum IL-8 levels and localization of IL-8 in liver from patients with chronic viral hepatitis. Hepatogastroenterology 45:1630–1634

    Google Scholar 

  15. Bezerra JA, Tiao G, Ryckman FC, Alonso M, Sabla GE, Shneider B, Sokol RJ, Aronow BJ (2002) Genetic induction of proinflammatory immunity in children with biliary atresia. Lancet 360:1653–1659

    Google Scholar 

  16. Baggiolini M, Dewald B, Moser B (1994) Interleukin-8 and related chemotactic cytokines CXC and CC chemokines. Adv Immunol 55:97–179

    Google Scholar 

  17. Rot A (1992) Endothelial cell binding of NAP-1/IL-8: role in neutrophil emigration. Immunol Today 13:291–294

    Google Scholar 

  18. Ogushi F, Tani K, Maniwa K, Ichikawa W, Tada H, Kawano T, Sone S (1997) Interleukin-8 in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis or idiopathic pulmonary fibrosis. J Med Invest 44:53–58

    Google Scholar 

  19. Brennan FM, Zachariae CO, Chantry D, Larsen CG, Turner M, Maini RN, Matsushima K, Feldmann M (1990) Detection of interleukin 8 biological activity in synovial fluids from patients with rheumatoid arthritis and production of interleukin 8 mRNA by isolated synovial cells. Eur J Immunol 20:2141–2144

    Google Scholar 

  20. Van Meir E, Ceska M, Effenberger F, Walz A, Grouzmann E, Desbaillets I, Frei K, Fontana A, de Tribolet N (1992) Interleukin-8 is produced in neoplastic and infectious diseases of the human central nervous system. Cancer Res 52:4297–4305

    Google Scholar 

  21. Halstensen A, Ceska M, Brandtzaeg P, Redl H, Naess A, Waage A (1993) Interleukin-8 in serum and cerebrospinal fluid from patients with meningococcal disease. J Infect Dis 167:471–475

    Google Scholar 

  22. al-Wabel A, al-Knawy B, Raziuddin S (1995) Interleukin-8 and granulocyte-macrophage colony-stimulating factor secretion in hepatocellular carcinoma and viral chronic active hepatitis. Clin Immunol Immunopathol 74:231–235

    Google Scholar 

  23. James LP, Farrar HC, Darville TL, Sullivan JE et al (2001) Elevation of serum interleukin 8 levels in acetaminophen overdose in children and adolescents. Clin Pharmacol Ther 70:280–286

    Google Scholar 

  24. Liu CS, Chin TW, Wei CF (1998) Value of gamma-glutamyl transpeptidase for early diagnosis of biliary atresia. Zhonghua Yi Xue Za Zhi (Taipei) 61:716–720

    Google Scholar 

  25. Endo M, Masuyama H, Watanabe K, Hagane K, Ikawa H, Yokoyama J, Kitajima M (1995) Calculation of biliary atresia prognostic index using a multivariate linear model. J Pediatr Surg 30:1575–1579

    Google Scholar 

  26. Thornton AJ, Strieter RM, Lindley I, Baggiolini M, Kunkel SL (1990) Cytokine-induced gene expression of a neutrophil chemotactic factor/IL-8 in human hepatocytes. J Immunol 144:2609–2613

    Google Scholar 

  27. Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ (2002) Mechanisms of hepatotoxicity. Toxicol Sci 65:166–176

    Google Scholar 

  28. Sokol RJ, Mack C, Narkewicz MR, Karrer FM (2003) Pathogenesis and outcome of biliary atresia: current concepts. J Pediatr Gastroenterol Nutr 37:4–21

    Google Scholar 

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Acknowledgements

This study was supported by a grant from the Ratchadapiseksompotch Fund, Faculty of Medicine, Center for Excellence Research Fund, Chulalongkorn University, and the Thailand Research Fund, Senior Research Scholar. The authors are greatly thankful to the staff of the Center of Excellence in Viral Hepatitis Research, Chulalongkorn University and Chulalongkorn Memorial Hospital for their dedicated efforts in this study. We also would like to thank Venerable Dr. Mettanando Bhikkhu of Wat Nakprok, Bangkok for reviewing the manuscript.

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Authors and Affiliations

  1. Department of Biochemistry, Chulalongkorn University, Bangkok, Thailand

    Sittisak Honsawek & Pisit Tangkijvanich

  2. Department of Surgery, Chulalongkorn University, Bangkok, Thailand

    Paisarn Vejchapipat

  3. Center of Excellence in Viral Hepatitis Research Unit, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Rama IV Road, Patumwan, Bangkok, Thailand, 10330

    Voranush Chongsrisawat, Nutchanart Thawornsuk & Yong Poovorawan

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  1. Sittisak Honsawek
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  2. Voranush Chongsrisawat
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Correspondence to Yong Poovorawan.

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Honsawek, S., Chongsrisawat, V., Vejchapipat, P. et al. Serum interleukin-8 in children with biliary atresia: relationship with disease stage and biochemical parameters. Ped Surgery Int 21, 73–77 (2005). https://doi.org/10.1007/s00383-004-1329-x

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