Abstract
Cytokines are low-molecular-weight proteinmediators that possess a wide spectrum of inflammatory,metabolic, and immunomodulatory properties. Cytokineshave been shown to be produced by monocytes/macrophages, lymphocytes, fibroblasts, endothelial cells,and more recently, hepatocytes and biliary epithelium.The aim of this study was to define biliary levels ofinterleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in patients undergoing endoscopicretrograde cholangiopancreatography (ERCP) in variousdisease states. Fifty-four patients undergoing ERCPcomprised the study group. IL-6 and TNF-α were measured in aspirated bile using an ELISAtechnique. Levels of both TNF-α and IL-6 weresignificantly higher in patients with cholangitis (P< 0.00001). Moreover, IL-6 was 100% specific forcholangitis since none of the patients without bacterialcholangitis — including patients with biliaryobstruction secondary to cholangiocarcinoma orpancreatic carcinoma — had measurable IL-6 intheir bile. Low levels of biliary TNF-α were detectable in fivepatients without cholangitis; the sensitivity andspecificity of TNF-α for cholangitis were 100% and82%, respectively. There was a strong statisticalcorrelation between biliary IL-6 and TNF-α levels (r= 0.819, P < 0.0001). In contrast, the correlationsbetween biliary cytokines and serum biochemicalparameters were weak. These results suggest that IL-6and TNF-α are sensitive markers for cholangitis and maydifferentiate it from other types of biliary tractdisease.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Tilg H, Wilmer A, Vogel W, Herold M, Nolchen B, Judmaier G, Huber C: Serum levels of cytokines in chronic liver diseases. Gastroenterology 103:264–274, 1992
Ramsey AJ, Ruby J, Ramshaw IA: A case for cytokines as effector molecules in the resolution of virus infection. Immunol Today 14:155–158, 1993
Matsumoto K, Fujii H, Michalopoulos G, Fung JJ, Demetris AJ: Human biliary epithelial cells secrete and respond to cytokines and hepatocyte growth factors in vitro. Hepatology 20:376–382, 1994
Byl B, Roucloux I, Crusiaux A, Dupont E, Deviere J: Tumor necrosis factor alpha and interleukin-6 plasma levels in infected cirrhotic patients. Gastroenterology 104:1492–1497, 1993
Roelofsen H, VanDerVeere CN, Ottenhoff R, et al: Decreased bilirubin transport in the perfused liver of endotoxemic rats. Gastroenterology 107:1075–1084, 1994
Tracey KJ, Beutler B, Lowry SF, Merryweather J, Wolpe S, Milsark IW, et al: Shock and tissue injury induced by recombinant human cachexin. Science 234:470–474, 1986
Chrousos GP: Cytokine therapy in septic shock. N Engl J Med 333:942–943, 1995
Schindler R, Mancilla J, Endres S, et al: Correlations and interactions in the production of IL-6, Il-1, and TNF in human blood mononuclear cells: IL-6 suppress IL-1 and TNF. Blood 75:40–47, 1990
Hill DB, Marsano L, Cohen D, Allen J, Shedlovsky S, McClain CJ: Increased plasma interleukin-6 concentrations in alcoholic hepatitis. J Lab Clin Med 119:547–552, 1992
McClain C, Hill D, Schmidt J, Diehl AM: Cytokines and alcoholic liver disease. Semin Liver Dis 13:170–182, 1993
Cominelli F, Nast CC, Duchini A, Lee M: Recombinant interleukin-1 receptor antagonist blocks the proinflammatory activity of endogenous interleukin-1 in rabbit immune colitis. Gastroenterology 103:65–71, 1992
Gionchetti P, Vaira D, Campieri M, Holton J, Menegatti M, Belluzi A, et al: Enhanced mucosal interleukin-6 and-8 in Helicobater pyloria-positive dyspeptic patients. Am J Gastroenterol 89:883–887, 1994
Kusske AM, Rongione AJ, Reber HA: Cytokines and acute pancreatitis. Gastroenterology 110:639–642, 1996
Bemelmans MH, Greve JW, Gouma DJ, Buurman WA: Increased concentrations of tumor necrosis factor and soluble TNF receptors in biliary obstruction in mice; soluble TNF receptors as prognostic factors for mortality. Gut 38:447–453, 1996
Whiting JF, Green RM, Rosenbluth AB, Gollan JL: Tumor necrosis factor-alpha decreases hepatocyte bile salt uptake and mediates endotoxin-induced cholestasis. Hepatology 22:1273–1278, 1995
Rosen HR, Lebow LT, LePage E, Demetriou AA: Plasma cytokine levels in patients with fulminant hepatic failure treated with a bioartificial liver. Gastroenterology 106(4):A971, 1994
Andus T, Gross V, Holstege A, et al: High concentrations of soluble tumor necrosis factor receptors in ascites. Hepatology 16:749–755, 1992
Engleberts I, Stephens S, Francot GJM, Van der Linden CJ, Buurman WA: Evidence of different effects of soluble TNF-receptors on various TNF measurements in human biological fluids. Lancet 338:515–516, 1991
Whiting JF, Green RM, Rosenbluth AB, Gollan JL: Tumor necrosis factor-alpha decrease hepatocyte bile salt uptake and mediates endotoxin-induced cholestasis. Hepatology 22:1273–1278, 1995
Moseley RH: Sepsis-associated cholestasis. Gastroenterology 112:302–306, 1997
Fong Y, Moldawer LL, Shires GT, Lowry SF: The biologic characteristics of cytokines and their implication in surgical injury. Surg Gynecol Obstet 170:363–378, 1990
Houssiau FA, Devogelaer JP, Van Damme J, De Deuxchaisnes CN, Van Snick J: Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides. Arthritis Rheum 31:784–788, 1988
Wollvekamp MCJ, Marquet RL: Interleukin-6: Historical background, genetics and biological significance. Immunol Lett 24:1–10, 1990
Rights and permissions
About this article
Cite this article
Rosen, H.R., Winkle, P.J., Kendall, B.J. et al. Biliary Interleukin-6 and Tumor Necrosis Factor-α in Patients Undergoing Endoscopic Retrograde Cholangiopancreatography. Dig Dis Sci 42, 1290–1294 (1997). https://doi.org/10.1023/A:1018822628096
Issue Date:
DOI: https://doi.org/10.1023/A:1018822628096