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Serum levels of cytokines in patients with colorectal cancer: Possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis

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Abstract

Serum levels of interleukin-1 (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured preoperatively in 24 patients with colorectal cancer. IL-1β was not elevated, IL-6 and IL-8 were markedly elevated, and GM-CSF was slightly elevated. TNF-α was not detected in most patients. Serum IL-6 levels correlated closely with serum IL-8 levels and with serum carbohydrate antigen (CA) 19-9 levels. Serum IL-6 levels were significantly higher in patients whose tumors exceeding 5.0 cm in diameter or spreading circumferentially. Serum IL-8 levels showed significant differences according to histological type, being lower in well differentiated adenocarcinoma compared to other types. Serum levels of IL-6 and IL-8 were significantly higher in patients with liver metastasis than in those without liver metastasis and serum levels of both these cytokines were also significantly higher in patients with lung metastasis than in those without lung metastasis. These results suggest that IL-6 and IL-8 may play an important role in the hematogenous metastasis of colorectal cancer.

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References

  1. Balkwill FR, Burke F. The cytokine network. Immunol Today 1989;9:299–304.

    Google Scholar 

  2. O'Garra A. Interleukins and the immune system 2. Lancet 1989;I:1003–1005.

    Google Scholar 

  3. Arai K, Lee F, Miyajima A, et al. Cytokines: Coordinators of immune and inflammatory responses. Annu Rev Biochem 1990; 59:783–836.

    Article  CAS  PubMed  Google Scholar 

  4. Dinarello CA. Interleukin-1 and the pathogenesis of the acutephase response. N Engl J Med 1984;311:1413–1418.

    CAS  PubMed  Google Scholar 

  5. Tracey KJ, Beutler B, Lowry SF, et al. Shock and tissue injury induced by recombinant human cachectin. Science 1986;234:470–474.

    CAS  PubMed  Google Scholar 

  6. Tracey KJ, Fong Y, Hesse D, et al. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteremia. Nature 1987;330:662–664.

    Article  CAS  PubMed  Google Scholar 

  7. Nijsten MWN, De Groot ER, Ten Duis HJ, et al. Serum levels of interleukin-6 and acute phase response. Lancet 1987;II:921.

    Google Scholar 

  8. Waage A, Halstensen A, Espevik T. Association between tumor necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet 1987;I:355–357.

    Google Scholar 

  9. Damas P, Reuter A, Gysen P, et al. Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans. Crit Care Med 1989;17:975–978

    CAS  PubMed  Google Scholar 

  10. Nishimoto N, Yoshizaki K, Tagoh H, et al. Elevation of serum interleukin-6 prior to acute phase proteins on the inflammation by surgical operation. Clin Immunol Immunopathol 1989;50: 399–401

    Article  CAS  PubMed  Google Scholar 

  11. Leser HG, Gross V, Scheibenbogen C, et al. Elevation of serum interleukin-6 concentration precedes acute-phase response and reflects severity in acute pancreatitis. Gastroenterology 1991;101:782–785

    CAS  PubMed  Google Scholar 

  12. Damas P, Ledoux D, Nys M, et al. Cytokine serum level during severe sepsis in human IL-6 as a marker of severity. Ann Surg 1992;215:356–362

    CAS  PubMed  Google Scholar 

  13. Sakamoto K, Egami H, Yoshimura R, et al. Colony-Stimulating factor producing carcinoma of the gallbladder. Jpn J Clin Oncol 1986;16:87–96

    CAS  PubMed  Google Scholar 

  14. Kawano M, Hirano T, Matsuda T, et al. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature 1988;332:83–85

    Article  CAS  PubMed  Google Scholar 

  15. Van Meir E, Sawamura Y, Diserens AC, et al. Human glioblastoma cells release interleukin 6 in vivo and in vitro. Cancer Res 1990;50:6683–6688

    PubMed  Google Scholar 

  16. Watson JM, Sensintaffar JL, Berek JS, et al. Constitutive production of interleukin 6 by ovarian cancer cell lines and by primary ovarian tumor cultures. Cancer Res 1990;50:6959–6965

    CAS  PubMed  Google Scholar 

  17. Siegall CB, Schwab G, Nordan RP, et al. Expression of the interleukin 6 receptor and interleukin 6 in prostate carcinoma cells. Cancer Res 1990;50:7786–7788

    CAS  PubMed  Google Scholar 

  18. Takenawa J, Kaneko Y, Fukumoto M, et al. Enhanced expression of interleukin-6 in primary human renal cell carcinomas. J Natl Cancer Inst 1991;83:1668–1672

    CAS  PubMed  Google Scholar 

  19. Naylor MS, Stamp GWH, Foulkes WD, et al. Tumor necrosis factor and its receptors in human ovarian cancer. J Clin Invest 1993;91:2194–2206

    CAS  PubMed  Google Scholar 

  20. Scuderi P, Lam KS, Ryan KJ, et al. Raised serum levels of tumor neerosis factor in parasitic infections. Lancet 1986;II: 1364–1365

    Google Scholar 

  21. Teppo AM, Maury CPJ. Radioimmunoassay of tumor necrosis factor in serum. Clin Chem 1987;33:2024–2027

    CAS  PubMed  Google Scholar 

  22. Balkwill F, Burke F, Talbot D, et al. Evidence for tumor neerosis factor eachectin production in cancer. Lancet 1987;II: 1229–1232

    Google Scholar 

  23. Socher SH, not detectable in patients with clinical cancer cachexia. J Natl Cancer Inst 1988;80:595–598

    CAS  PubMed  Google Scholar 

  24. Fearon KCH, McMillan DC, Preston T, et al. Elevated circulating interleukin-6 is associated with an acute-phase response but reduced fixed hepatic protein synthesis in patients with cancer. Ann Surg 1991;213:26–31

    CAS  PubMed  Google Scholar 

  25. Japanese Research Society for Cancer of Colon and Rectum. General rules for clinical and pathological studies on cancer of colon, rectum, and anus. 4th ed. Tokyo: Kanehara Shuppan, 1985

    Google Scholar 

  26. American Joint Committee on Cancer, Manual for staging of cancer. 3rd ed, Philadelphia: JB Lippincott, 1987

    Google Scholar 

  27. Hermanek P, Sobin LH (eds) TNM classification of malignant tumors (International Union Against Cancer). 4th ed. Berlin: Springer, 1987

    Google Scholar 

  28. Gross V, Andus T, Caesar I, et al. Evidence for continuous stimulation of interleukin-6 production in Crohn's disease. Gastroenterology 1992;102:514–519

    CAS  PubMed  Google Scholar 

  29. Izzo RS, Witkon K, Chen AI, et al. Interleukin-8 and neutrophil markers in colonic mucosa from patients with ulcerative colitis. Am J Gastroenterol 1992;87:1447–1452

    CAS  PubMed  Google Scholar 

  30. Isaacs KL, Sartor RB, Haskill S. Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification. Gastroenterology 1992; 103:1587–1595

    CAS  PubMed  Google Scholar 

  31. Hyams JS, Fitzgerald JE, Treem WR, et al. Relationship of functional and antigenic interleukin 6 to disease activity in inflammatory bowel disease. Gastroenterology 1993;104: 1285–1292

    CAS  PubMed  Google Scholar 

  32. Shalaby MR, Waage A, Aarden L, et al. Endotoxin, tumor necrosis factor-α and interleukin 1 induce interleukin 6 production in vivo. Clin Immunol Immunopathol 1989;53:488–498

    Article  CAS  PubMed  Google Scholar 

  33. Fong Y, Tracey KJ, Moldawer LL, et al. Antibodies to cachectin/ tumor necrosis factor reduce interleukin 1β and interleukin 6 appearance during lethal bacteremia. J Exp Med 1989;170: 1627–1633

    Article  CAS  PubMed  Google Scholar 

  34. Isshiki H, Akira S, Tanabe O, et al. Constitutive and interleukin-1 (IL-1)-inducible factors interact with the IL-1-responsive clement in the IL-6 gene. Mol Cell Biol 1990;10:2757–2764

    CAS  PubMed  Google Scholar 

  35. Matsushima K, Oppenheim JJ. Interleukin-8 and MCAF: Novel inflammatory cytokines inducible by IL-1 and TNF. Cytokine 1989;1:1–12

    Article  Google Scholar 

  36. Natali P, Nicotra MR, Cavaliere R, et al. Differential expression of intercellular adhesion molecule 1 in primary and metastatic melanoma lesions. Cancer Res 1990;50:1271–1278

    CAS  PubMed  Google Scholar 

  37. Tsujisaki M, Imai K, Hirata H, et al. Detection of circulating adhesion molecule-1 antigen in malignant diseases. Clin Exp Immunol 1991;85:3–8

    CAS  PubMed  Google Scholar 

  38. Takada A, Ohmori K, Yoneda T, et al. Contribution of carbohydrate antigens sialyl Lewis A and sialyl Lewis X to adhesion of human cancer cells to vascular endothelium. Cancer Res 1993;53:354–361

    CAS  PubMed  Google Scholar 

  39. Dejane E, Bertocchi F, Bortolami MC, et al. Interleukin 1 promotes tumor cell adhesion to cultured human endothelial cells. J Clin Invest 1988;82:1466–1470

    Google Scholar 

  40. Larson CG, Anderson AD, Apella E, et al. The neutrophilactivating protein (NAP-1) is also chemotactic for T lymphocytes. Science 1989;243:1464–1466

    Google Scholar 

  41. Strieter RM, Kunkel SL, Showell HL, et al. Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-α, LPS, and IL-1β. Science 1989;243:1467–1469

    CAS  PubMed  Google Scholar 

  42. Paccaud JP, Shifferli JA, Baggiolini M. NAP-1/IL-8 induces upregulation of CR1 receptors in human neutrophil leukocytes. Biochem Biophys Res Commun 1990;166:187–192

    Article  CAS  PubMed  Google Scholar 

  43. Detmers PA, Lo SK, Olsen-Egbert E, et al. Neutrophil activating protein 1/interleukin 8 stimulates the binding activity of the leukocyte adhesion receptor CD11b/CD18 on human neutrophils. J Exp Med 1990;171:1152–1162

    Article  Google Scholar 

  44. Takeda A, Ohmori K, Takahashi N, et al. Adhesion of human cancer cells to vascular endothelium mediated by a carbohydrate antigen, sialyl Lewis A. Biochem Biophys Res Commun 1991; 179:713–719

    Article  Google Scholar 

  45. Berg EL, Robinson MK, Mansson O, et al. A carbohydrate domain common to both sialyl Lea and sialyl Lex is recognized by the endothelial cell leukocyte adhesion molecule ELAM-1. J Biol Chem 1991;266:14869–14872

    CAS  PubMed  Google Scholar 

  46. Fabian I, Baldwin GC, Golde DW, et al. Biosynthetic granulocyte-macrophage colony-stimulating factor enhances neutrophil cytotoxicity toward human leukemia cells. Leukemia 1987;1:613–617

    CAS  PubMed  Google Scholar 

  47. Grabstein KH, Urdal DL, Tushinski RJ, et al. Induction of macrophage tumoricidal activity by granulocyte-macrophage colony-stimulating factor. Science 1986;232:506–508

    CAS  PubMed  Google Scholar 

  48. Takeda K, Hatakeyama K, Tsuchiya Y, et al. A correlation between GM-CSF gene expression and metastases in murine tumors. Int J Cancer 1991;47:413–420

    CAS  PubMed  Google Scholar 

  49. Young MRI, Lozano Y, Coogan M, et al. Stimulation of the metastatic properties of Lewis lung carcinoma cells by autologous granulocyte-macrophage colony-stimulating factor. Int J Cancer 1992;50:628–634

    CAS  PubMed  Google Scholar 

  50. Takeda K, Fujii N, Nitta Y, et al. Murine tumor cells metastasizing selectively in the liver: Ability to produce hepatocyteactivating cytokines interleukin-1 and/or-6. Jpn J Cancer Res 1991;82:1299–1308

    CAS  PubMed  Google Scholar 

  51. Carswell EA, Old LJ, Kassel RL, et al. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 1975;72:3666–3670

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Kobe Rosai Hospital of the Labour Welfare Corporation, 4-1-23 Kagoike-dori, Chuo-ku, 651, Kobe, Japan

    Takashi Ueda, Etsuji Shimada & Tomoaki Urakawa

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  1. Takashi Ueda
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  2. Etsuji Shimada
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  3. Tomoaki Urakawa
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Ueda, T., Shimada, E. & Urakawa, T. Serum levels of cytokines in patients with colorectal cancer: Possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis. J Gastroenterol 29, 423–429 (1994). https://doi.org/10.1007/BF02361238

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