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Published in: Digestive Diseases and Sciences 7/2010

01-07-2010 | Original Article

Adipokines and Cytokines in Human Pancreatic Juice: Unraveling the Local Pancreatic Inflammatory Milieu

Authors: Kathryn M. Dalbec, C. Max Schmidt, Terence E. Wade, Sue Wang, Deborah A. Swartz-Basile, Henry A. Pitt, Nicholas J. Zyromski

Published in: Digestive Diseases and Sciences | Issue 7/2010

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Abstract

Background

Differential adipokine expression in obesity influences the inflammatory milieu, and may explain in part obesity’s negative impact on pancreatic disease. Pancreatic juice analysis may provide a good means to evaluate the local pancreatic inflammatory milieu. The presence of adipokines in pancreatic juice is unknown.

Aims

This proof-of-concept study was designed to determine the presence of adipokines and cytokines in human pancreatic juice.

Methods

With institutional review board approval, pancreatic juice was obtained from ten patients with a broad range of diagnoses at the time of endoscopic retrograde cholangiopancreatography. Pancreatic juice was assayed using enzyme-linked immunosorbent assay (ELISA) for insulin, the proinflammatory adipokine leptin, the anti-inflammatory adipokine adiponectin, and the inflammatory mediators interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). Correlation between adipokine and inflammatory mediator expression was determined by linear regression analysis. Data are presented as mean ± standard error of the mean (SEM); P < 0.05 was considered statistically significant.

Results

Leptin (0.16 ± 0.05 ng/ml) and adiponectin (0.63 ± 0.02 μg/ml) were both present, as were the inflammatory mediators IL-6 (112.6 ± 28.1 pg/ml), TNF-α (49.0 ± 18.8 pg/ml), and MCP-1 (32.2 ± 0.9 pg/ml). Paradoxically, the expression of the anti-inflammatory adipokine adiponectin correlated strongly with that of the proinflammatory cytokine IL-6 (R 2 = 0.98, P < 0.001).

Conclusions

This report is the first to describe adipokine expression in human pancreatic juice. Human pancreatic juice inflammatory mediators and adipokines may provide an important measurement of the local pancreatic inflammatory milieu.
Literature
1.
go back to reference Shi C, et al. Immune status and inflammatory response differ locally and systemically in severe acute pancreatitis. Scand J Gastroenterol. 2006;41(4):472–480.CrossRefPubMed Shi C, et al. Immune status and inflammatory response differ locally and systemically in severe acute pancreatitis. Scand J Gastroenterol. 2006;41(4):472–480.CrossRefPubMed
2.
go back to reference Norman J. The role of cytokines in the pathogenesis of acute pancreatitis. Am J Surg. 1998;175(1):76–83.CrossRefPubMed Norman J. The role of cytokines in the pathogenesis of acute pancreatitis. Am J Surg. 1998;175(1):76–83.CrossRefPubMed
3.
go back to reference Denyer ME, Cotton PB. Pure pancreatic juice studies in normal subjects and patients with chronic pancreatitis. Gut. 1979;20(2):89–97.CrossRefPubMed Denyer ME, Cotton PB. Pure pancreatic juice studies in normal subjects and patients with chronic pancreatitis. Gut. 1979;20(2):89–97.CrossRefPubMed
4.
go back to reference Kuhlmann KF, et al. Evaluation of matrix metalloproteinase 7 in plasma and pancreatic juice as a biomarker for pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2007;16(5):886–891.CrossRefPubMed Kuhlmann KF, et al. Evaluation of matrix metalloproteinase 7 in plasma and pancreatic juice as a biomarker for pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2007;16(5):886–891.CrossRefPubMed
5.
go back to reference Matsumoto S, et al. Evaluation of cytology and tumor markers of pure pancreatic juice for the diagnosis of pancreatic cancer at early stages. Pancreas. 1994;9(6):741–747.CrossRefPubMed Matsumoto S, et al. Evaluation of cytology and tumor markers of pure pancreatic juice for the diagnosis of pancreatic cancer at early stages. Pancreas. 1994;9(6):741–747.CrossRefPubMed
6.
7.
go back to reference Segersvard R, et al. Obesity alters cytokine gene expression and promotes liver injury in rats with acute pancreatitis. Obesity. 2008;16(1):23–28.CrossRefPubMed Segersvard R, et al. Obesity alters cytokine gene expression and promotes liver injury in rats with acute pancreatitis. Obesity. 2008;16(1):23–28.CrossRefPubMed
8.
go back to reference Zyromski NJ, et al. A murine model of obesity implicates the adipokine milieu in the pathogenesis of severe acute pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2008;295(3):G552–G558.CrossRefPubMed Zyromski NJ, et al. A murine model of obesity implicates the adipokine milieu in the pathogenesis of severe acute pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2008;295(3):G552–G558.CrossRefPubMed
9.
go back to reference Mathur AZN, Pitt H, Al-Azzawi H, Walker J, Saxena R, Lillemoe K. Pancreatic steatosis promotes dissemination and lethality of pancratic cancer. J Am Coll Surg. 2009 (in press). Mathur AZN, Pitt H, Al-Azzawi H, Walker J, Saxena R, Lillemoe K. Pancreatic steatosis promotes dissemination and lethality of pancratic cancer. J Am Coll Surg. 2009 (in press).
10.
go back to reference Araki H, et al. Adiponectin plays a protective role in caerulein-induced acute pancreatitis in mice fed a high-fat diet. Gut. 2008;57(10):1431–1440.CrossRefPubMed Araki H, et al. Adiponectin plays a protective role in caerulein-induced acute pancreatitis in mice fed a high-fat diet. Gut. 2008;57(10):1431–1440.CrossRefPubMed
11.
go back to reference Chang MC, et al. Adiponectin as a potential differential marker to distinguish pancreatic cancer and chronic pancreatitis. Pancreas. 2007;35(1):16–21.CrossRefPubMed Chang MC, et al. Adiponectin as a potential differential marker to distinguish pancreatic cancer and chronic pancreatitis. Pancreas. 2007;35(1):16–21.CrossRefPubMed
12.
go back to reference Kelesidis I, Kelesidis T, Mantzoros CS. Adiponectin and cancer: a systematic review. Br J Cancer. 2006;94(9):1221–1225.CrossRefPubMed Kelesidis I, Kelesidis T, Mantzoros CS. Adiponectin and cancer: a systematic review. Br J Cancer. 2006;94(9):1221–1225.CrossRefPubMed
13.
go back to reference Lawrence AM, et al. Glucagon and insulin in pancreatic exocrine secretions. Lancet. 1979;1(8130):1354–1355.CrossRefPubMed Lawrence AM, et al. Glucagon and insulin in pancreatic exocrine secretions. Lancet. 1979;1(8130):1354–1355.CrossRefPubMed
14.
go back to reference Antuna-Puente B, et al. Adipokines: the missing link between insulin resistance and obesity. Diabetes Metab. 2008;34(1):2–11.PubMed Antuna-Puente B, et al. Adipokines: the missing link between insulin resistance and obesity. Diabetes Metab. 2008;34(1):2–11.PubMed
15.
go back to reference Conwell DL, et al. The effect of moderate sedation on exocrine pancreas function in normal healthy subjects: a prospective, randomized, cross-over trial using the synthetic porcine secretin stimulated Endoscopic Pancreatic Function Test (ePFT). Am J Gastroenterol. 2005;100(5):1161–1166.CrossRefPubMed Conwell DL, et al. The effect of moderate sedation on exocrine pancreas function in normal healthy subjects: a prospective, randomized, cross-over trial using the synthetic porcine secretin stimulated Endoscopic Pancreatic Function Test (ePFT). Am J Gastroenterol. 2005;100(5):1161–1166.CrossRefPubMed
16.
go back to reference Yoshida K, et al. Screening of genes specifically activated in the pancreatic juice ductal cells from the patients with pancreatic ductal carcinoma. Cancer Sci. 2003;94(3):263–270.CrossRefPubMed Yoshida K, et al. Screening of genes specifically activated in the pancreatic juice ductal cells from the patients with pancreatic ductal carcinoma. Cancer Sci. 2003;94(3):263–270.CrossRefPubMed
17.
go back to reference Gronborg M, et al. Comprehensive proteomic analysis of human pancreatic juice. J Proteome Res. 2004;3(5):1042–1055.CrossRefPubMed Gronborg M, et al. Comprehensive proteomic analysis of human pancreatic juice. J Proteome Res. 2004;3(5):1042–1055.CrossRefPubMed
18.
go back to reference Zhou L, et al. Comparative proteomic analysis of human pancreatic juice: methodological study. Proteomics. 2007;7(8):1345–1355.CrossRefPubMed Zhou L, et al. Comparative proteomic analysis of human pancreatic juice: methodological study. Proteomics. 2007;7(8):1345–1355.CrossRefPubMed
19.
go back to reference Chen R, et al. Comparison of pancreas juice proteins from cancer versus pancreatitis using quantitative proteomic analysis. Pancreas. 2007;34(1):70–79.CrossRefPubMed Chen R, et al. Comparison of pancreas juice proteins from cancer versus pancreatitis using quantitative proteomic analysis. Pancreas. 2007;34(1):70–79.CrossRefPubMed
20.
21.
go back to reference de Beaux AC, et al. Serum concentrations of inflammatory mediators related to organ failure in patients with acute pancreatitis. Br J Surg. 1996;83(3):349–353.CrossRefPubMed de Beaux AC, et al. Serum concentrations of inflammatory mediators related to organ failure in patients with acute pancreatitis. Br J Surg. 1996;83(3):349–353.CrossRefPubMed
22.
go back to reference Jablonowska M, et al. Immunohistochemical localization of interleukin-6 in human pancreatitis. Appl Immunohistochem Mol Morphol. 2008;16(1):40–43.PubMed Jablonowska M, et al. Immunohistochemical localization of interleukin-6 in human pancreatitis. Appl Immunohistochem Mol Morphol. 2008;16(1):40–43.PubMed
23.
go back to reference Yasuda H, et al. Cytokine expression and induction of acinar cell apoptosis after pancreatic duct ligation in mice. J Interferon Cytokine Res. 1999;19(6):637–644.CrossRefPubMed Yasuda H, et al. Cytokine expression and induction of acinar cell apoptosis after pancreatic duct ligation in mice. J Interferon Cytokine Res. 1999;19(6):637–644.CrossRefPubMed
24.
go back to reference Kazbay K, et al. Increased transforming growth factor beta in pure pancreatic juice in pancreatitis. Pancreas. 2001;22(2):193–195.CrossRefPubMed Kazbay K, et al. Increased transforming growth factor beta in pure pancreatic juice in pancreatitis. Pancreas. 2001;22(2):193–195.CrossRefPubMed
25.
go back to reference Noh KW, et al. Do cytokine concentrations in pancreatic juice predict the presence of pancreatic diseases? Clin Gastroenterol Hepatol. 2006;4(6):782–789.CrossRefPubMed Noh KW, et al. Do cytokine concentrations in pancreatic juice predict the presence of pancreatic diseases? Clin Gastroenterol Hepatol. 2006;4(6):782–789.CrossRefPubMed
26.
go back to reference Pungpapong S, et al. Endoscopic ultrasound and IL-8 in pancreatic juice to diagnose chronic pancreatitis. Pancreatology. 2007;7(5–6):491–496.CrossRefPubMed Pungpapong S, et al. Endoscopic ultrasound and IL-8 in pancreatic juice to diagnose chronic pancreatitis. Pancreatology. 2007;7(5–6):491–496.CrossRefPubMed
27.
go back to reference Chen CC, et al. Proinflammatory cytokines in early assessment of the prognosis of acute pancreatitis. Am J Gastroenterol. 1999;94(1):213–218.CrossRefPubMed Chen CC, et al. Proinflammatory cytokines in early assessment of the prognosis of acute pancreatitis. Am J Gastroenterol. 1999;94(1):213–218.CrossRefPubMed
28.
go back to reference Sathyanarayan G, et al. Elevated level of interleukin-6 predicts organ failure and severe disease in patients with acute pancreatitis. J Gastroenterol Hepatol. 2007;22(4):550–554.CrossRefPubMed Sathyanarayan G, et al. Elevated level of interleukin-6 predicts organ failure and severe disease in patients with acute pancreatitis. J Gastroenterol Hepatol. 2007;22(4):550–554.CrossRefPubMed
29.
go back to reference Naugler WE, et al. The wolf in sheep’s clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol Med. 2008;14(3):109–119.CrossRefPubMed Naugler WE, et al. The wolf in sheep’s clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol Med. 2008;14(3):109–119.CrossRefPubMed
30.
go back to reference Hoene M, Weigert C. The role of interleukin-6 in insulin resistance, body fat distribution and energy balance. Obes Rev. 2008;9(1):20–29.PubMed Hoene M, Weigert C. The role of interleukin-6 in insulin resistance, body fat distribution and energy balance. Obes Rev. 2008;9(1):20–29.PubMed
31.
go back to reference Sennello JA, et al. Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 2008;105(23):8085–8090. Sennello JA, et al. Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 2008;105(23):8085–8090.
32.
go back to reference Bastard J-P, et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw. 2006;17(1):4–12.PubMed Bastard J-P, et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw. 2006;17(1):4–12.PubMed
33.
go back to reference Kristiansen OP, Mandrup-Poulsen T. Interleukin-6, diabetes: the good, the bad, or the indifferent? Diabetes. 2005;54(Suppl 2):S114–S1124.CrossRefPubMed Kristiansen OP, Mandrup-Poulsen T. Interleukin-6, diabetes: the good, the bad, or the indifferent? Diabetes. 2005;54(Suppl 2):S114–S1124.CrossRefPubMed
34.
go back to reference Kern PA, et al. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab. 2001;280(5):E745–E751.PubMed Kern PA, et al. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab. 2001;280(5):E745–E751.PubMed
35.
go back to reference Carey AL, Febbraio MA. Interleukin-6 and insulin sensitivity: friend or foe? Diabetologia. 2004;47(7):1135–1142.CrossRefPubMed Carey AL, Febbraio MA. Interleukin-6 and insulin sensitivity: friend or foe? Diabetologia. 2004;47(7):1135–1142.CrossRefPubMed
Metadata
Title
Adipokines and Cytokines in Human Pancreatic Juice: Unraveling the Local Pancreatic Inflammatory Milieu
Authors
Kathryn M. Dalbec
C. Max Schmidt
Terence E. Wade
Sue Wang
Deborah A. Swartz-Basile
Henry A. Pitt
Nicholas J. Zyromski
Publication date
01-07-2010
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 7/2010
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-009-0977-z

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