ORIGINAL ARTICLE

JOP. J Pancreas (Online) 2004; 5(3):138-144.

Expression of Interleukin-8 in Human Obstructive Pancreatitis

Yoshiharu Motoo, Min-Jue Xie, Hisatsugu Mouri, Norio Sawabu

Department of Internal Medicine and Medical Oncology, Cancer Research Institute, Kanazawa University. Kanazawa, Japan

ABSTRACT

Context Obstructive pancreatitis is a specific form of pancreatitis, which is caused by the obstruction of the main pancreatic duct due to tumors or some other causes. Interleukin-8 is induced in acute pancreatitis, but its expression in obstructive pancreatitis has not been clarified.

Objective We attempted to provide some insight into the significance of interleukin -8 in the pathogenesis of pancreatic fibrosis.

Patients Fifteen cases of pancreatic cancer, 7 cases of mucinous cystadenoma, 3 cases of Vater’s papilla cancer and 9 normal pancreases were included in this study.

Main outcome measures The obstructive pancreatitis portions of the above pathologies were evaluated for interleukin-8 expression by means of immunohistochemistry and in situ hybridization.

Results Interleukin-8 was positive in 72% of cases of obstructive pancreatitis. The positive rate was not significantly related to the etiology of the obstruction (P=0.972). Interleukin-8 was expressed in infiltrating cells, proliferating ductular cells and acinar cells. In contrast, normal pancreases and tumor cells lacked interleukin-8 expression (P<0.001 vs. obstructive pancreatitis). Both immunohistochemistry and in situ hybridization demonstrated that interleukin-8 was expressed mostly in acinar cells in mild pancreatic fibrosis, whereas it was expressed in stromal and ductular cells in moderate and severe pancreatic fibrosis.

Conclusions These results suggest that interleukin-8 expression is related to the fibrotic process in obstructive pancreatitis.

Full text: HTML format   PDF format
  Look up who cited this article

References

  1. Baggiolini M, Walz A, Kunkel SL. Neutrophil-activating peptide-1/ interluekin-8, novel cytokine that activates neutrophils. J Clin Invest 1989; 84:1045-9. [More details]

  2. Rajarathnam K, Sykes BD, Kay CM, Dewald B, Geiser T, Baggiolini M, Clark-Lewis I. Neutrophil activation by monomeric interleukin-8. Science 1994; 264:90-2. [More details]

  3. Watanabe K, Suematsu M, Iida M, Takaishi K, Iizuka Y, Suzuki H, et al. Effect of rat CINC/gro, a member of the interleukin-8 family, on leukocytes in microcirculation of the rat mesentery. Exp Mol Pathol 1992; 56:60-9. [More details]

  4. Yamada H, Takahashi S, Fujita H, Kobayashi N, Okabe S. Cytokine-induced neutrophil chemoattractants in healing of gastric ulcers in rats. Dig Dis Sci 1999; 44:889-95. [More details]

  5. Matsumura F, Yamaguchi Y, Goto M, Ichiguchi O, Akizuki E, Matsuda T, et al. Xanthine oxidase inhibition attenuates Kupffer cell production of neutrophil chemoattractant following ischemia-reperfusion in rat liver. Hepatology 1998; 28:1578-87. [More details]

  6. Osman MO, Kristensen JU, Jacobsen NO, Lausten SB, Deleuran B, Deleuran M, et al. A monoclonal anti-inteleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits. Gut 1998; 43:232-9. [More details]

  7. Pezzilli R, Billi P, Miniero R, Fiocchi M, Cappelletti O, Morselli-Labate AM, et al. Serum interleukin-6, interleukin-8, and beta 2-microglobulin in early assessment of severity of acute pancreatitis. Comparison with serum C-reactive protein. Dig Dis Sci 1995; 40:2341-8. [More details]

  8. Rau B, Steinbach G, Gansauge F, Mayer JM, Grunert A, Beger HG. The potential role of procalcitonin and interleukin-8 in the prediction of infected necrosis in acute pancreatitis. Gut 1997; 41:832-40. [More details]

  9. Saurer L, Reber P, Schaffner T, Buchler MW, Buri C, Kappeler A, et al. Differential expression of chemokines in normal pancreas and in chronic pancreatitis. Gastroenterology 2000; 118:356-67. [More details]

  10. Di Sebastiano P, di Mola FF, Di Febbo C, Baccante G, Porreca E, Innocenti P, et al. Expression of interleukin 8 (IL-8) and substance P in human chronic pancreatitis. Gut 2000; 47:423-8. [More details]

  11. Lankisch PG, Banks PA. Chronic pancreatitis: etiology. In: Pancreatitis. Lankisch PG, Banks PA, eds. Berlin, Germany: Springer-Verlag, 1993:199-206. [More details]

  12. Singh SM, Reber HA. The pathology of chronic pancreatitis. World J Surg 1990; 14:2-10. [More details]

  13. Bazzoni F, Cassatella MA, Rossi F, Ceska M, Dewald B, Baggiolini M. Phagocytosing neutrophils produce and release high amounts of the neutrophil-activating peptide 1/interleukin 8. J Exp Med 1991; 173:771-4. [More details]

  14. Afford SC, Fisher NC, Neil DA, Fear J, Brun P, Hubscher SG, Adams DH. Distinct patterns of chemokine expression are associated with leukocyte recruitment in alcoholic hepatitis and alcoholic cirrhosis. J Pathol 1998; 186:82-9. [More details]

  15. Carre PC, Mortenson RL, King TE Jr, Noble PW, Sable CL, Riches DW. Increased expression of the interleukin-8 gene by alveolar macrophages in idiopathic pulmonary fibrosis. A potential mechanism for the recruitment and activation of neutrophils in lung fibrosis. J Clin Invest 1991; 88:1802-10. [More details]

  16. Tabary O, Escotte S, Couetil JP, Hubert D, Dusser D, Puchelle E, Jacquot J. Genistein inhibits constitutive and inducible NF-KappaB activation and decreases IL-8 production by human cystic fibrosis bronchial gland cells. Am J Pathol 1999; 155:473-81. [More details]

  17. Andoh A, Takaya H, Saotome T, Shimada M, Hata K, Araki Y, et al. Cytokine regulation of chemokine (IL-8, MCP-1, and RANTES) gene expression in human pancreatic periacinar myofibroblasts. Gastroenterology 2000; 119:211-9. [More details]

  18. Mazzucchelli L, Hauser C, Zgraggen K, Wagner H, Hess M, Laissue JA, Mueller C. Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation. Am J Pathol 1994; 144:997-1007. [More details]

  19. Shi Q, Abbruzzese JL, Huang S, Fidler IJ, Xiong Q, Xie K. Constitutive and inducible interleukin 8 expression by hypoxia and acidosis renders human pancreatic cancer cells more tumorigenic and metastatic. Clin Cancer Res 1999; 5:3711-21. [More details]

  20. Vickers SM, MacMillan-Crow LA, Green M, Ellis C, Thompson JA. Association of increased immunostaining for inducible nitric oxide synthase and nitrotyrosine with fibroblast growth factor transformation in pancreatic cancer. Arch Surg 1999; 134:245-51. [More details]

  21. Ganesh Pai C, Sreejayan, Rao MN. Evidence for oxidant stress in chronic pancreatitis. Indian J Gastroenterol 1999; 18:156-7. [More details]

  22. Kanazawa H, Shoji S, Yoshikawa T, Hirata K, Yoshikawa J. Increased production of endogenous nitric oxide in patients with bronchial asthma and chronic obstructive pulmonary disease. Clin Exp Allergy 1998; 28:1244-50. [More details]

  23. Di Sebastiano P, di Mola FF, Bockman DE, Friess H, Buchler MW. Chronic pancreatitis: the perspective of pain generation by neuroimmune interaction. Gut 2003; 52:907-11. [More details]

Keywords Fibrosis; Gene Expression Profiling; Immunohistochemistry; In Situ Hybridization; Interleukin-8; Pancreatic Diseases; Pancreatitis

Correspondence Yoshiharu Motoo: motoo@kenroku.kanazawa-u.ac.jp