Top

International Journal of Colorectal Disease

Published in:

01-02-2010 | Review

Serum interleukin-6 levels in colorectal cancer patients—a summary of published results

Authors: Heike Knüpfer, Rainer Preiss

Published in: International Journal of Colorectal Disease | Issue 2/2010

Abstract

Introduction

It is now clear that inflammation and cancer initiation and progression are linked. Interleukin-6 (IL-6) is a pleiotropic inflammatory cytokine with described cancer stimulatory and also cancer inhibitory properties. The study’s aim was to assess the potential of circulating IL-6 as a prognostic indicator in colorectal cancer.

Materials and methods

A literature search was conducted using PubMed, restricted to articles published in English language. We compared published results in regard to differences in IL-6 levels between healthy controls and colon cancer patients (seven published results), between patients with increasing tumor stages (eight published results), between patients with differences in tumor size (four published results), and between patients with and without liver (three published results) or lung metastasis (one published result). Furthermore, we reviewed the literature in regard to the possible correlation of IL-6 levels with survival time (five published results) and correlation of IL-6 levels and lymph node involvement (three published results).

Results

Concerning colon tumors, results are consistent. Colon cancer patients reveal higher serum IL-6 levels than healthy controls. Furthermore, higher IL-6 levels are associated with increasing tumor stages and tumor size, with metastasis and decreased survival.

Conclusion

Therefore, circulating IL-6 might be prognostic indicator in colorectal cancer.

Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G, Schaper F (2003) Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374(1):1–20 ReviewCrossRefPubMed

Lust JA, Donovan KA, Kline MP, Greipp PR, Kyle RA, Maihle NJ (1992) Isolation of an mRNA encoding a soluble form of the human interleukin-6 receptor. Cytokine 4:96–100CrossRefPubMed

Rose-John S, Waetzig GH, Scheller J, Grötzinger J, Seegert D (2007) The IL-6/sIL-6R complex as a novel target for therapeutic approaches. Expert Opin Ther Targets 11:613–624CrossRefPubMed

Althoff K, Mullberg J, Aasland D, Voltz N, Kallen K, Grotzinger J, Rose-John S (2001) Recognition sequences and structural elements contribute to shedding susceptibility of membrane proteins. Biochem J 353(Pt 3):663–672CrossRefPubMed

Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, Hirano T, Kishimoto T (1989) Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell 58:573–581CrossRefPubMed

Mackiewicz A, Schooltink H, Heinrich PC, Rose-John S (1992) Complex of soluble human IL-6-receptor/IL-6 up-regulates expression of acute-phase proteins. J Immunol 149:2021–2027PubMed

Rose-John S, Schooltink H (2007) Cytokines are a therapeutic target for the prevention of inflammation-induced cancers. Recent Results Cancer Res 174:57–66CrossRefPubMed

Hirano T, Ishihara K, Hibi M (2000) Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene 19:2548–2556CrossRefPubMed

Schindler CW (2002) Series introduction. JAK-STAT signaling in human disease. J Clin Invest 109:1133–1137PubMed

10.

Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, Darnell JE Jr (1999) Stat3 as an oncogene. Cell 98:295–303CrossRefPubMed

11.

Schneider MR, Hoeflich A, Fischer JR, Wolf E, Sordat B, Lahm H (2000) Interleukin-6 stimulates clonogenic growth of primary and metastatic human colon carcinoma cells. Cancer Lett 151:31–38CrossRefPubMed

12.

Hsu CP, Chung YC (2006) Influence of interleukin-6 on the invasiveness of human colorectal carcinoma. Anticancer Res 26:4607–4614PubMed

13.

Brozek W, Bises G, Girsch T, Cross HS, Kaiser HE, Peterlik M (2005) Differentiation-dependent expression and mitogenic action of interleukin-6 in human colon carcinoma cells: relevance for tumour progression. Eur J Cancer 41:2347–2354CrossRefPubMed

14.

Brozek W, Bises G, Fabjani G, Cross HS, Peterlik M (2008) Clone-specific expression, transcriptional regulation, and action of interleukin-6 in human colon carcinoma cells. BMC Cancer 8:13CrossRefPubMed

15.

Becker C, Fantini MC, Wirtz S, Nikolaev A, Lehr HA, Galle PR, Rose-John S, Neurath MF (2005) IL-6 signaling promotes tumor growth in colorectal cancer. Cell Cycle 4:217–220PubMed

16.

Becker C, Fantini MC, Schramm C, Lehr HA, Wirtz S, Nikolaev A, Burg J, Strand S, Kiesslich R, Huber S, Ito H, Nishimoto N, Yoshizaki K, Kishimoto T, Galle PR, Blessing M, Rose-John S, Neurath MF (2004) TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 21:491–501CrossRefPubMed

17.

Galizia G, Orditura M, Romano C, Lieto E, Castellano P, Pelosio L, Imperatore V, Catalano G, Pignatelli C, De Vita F (2002) Prognostic significance of circulating IL-10 and IL-6 serum levels in colon cancer patients undergoing surgery. Clin Immunol 102:169–178CrossRefPubMed

18.

Dymicka-Piekarska V, Matowicka-Karna J, Gryko M, Kemona-Chetnik I, Kemona H (2007) Relationship between soluble P-selectin and inflammatory factors (interleukin-6 and C-reactive protein) in colorectal cancer. Thromb Res 20:585–590CrossRef

19.

Kinoshita T, Ito H, Miki C (1999) Serum interleukin-6 level reflects the tumor proliferative activity in patients with colorectal carcinoma. Cancer 85:2526–2531CrossRefPubMed

20.

Chung YC, Chang YF (2003) Serum interleukin-6 levels reflect the disease status of colorectal cancer. J Surg Oncol 83:222–226CrossRefPubMed

21.

Ueda T, Shimada E, Urakawa T (1994) Serum levels of cytokines in patients with colorectal cancer: possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis. J Gastroenterol 29:423–429CrossRefPubMed

22.

Nikiteas NI, Tzanakis N, Gazouli M, Rallis G, Daniilidis K, Theodoropoulos G, Kostakis A, Peros G (2005) Serum IL-6, TNFalpha and CRP levels in Greek colorectal cancer patients: prognostic implications. World J Gastroenterol 11:1639–1643PubMed

23.

Kaminska J, Nowacki MP, Kowalska M, Rysinska A, Chwalinski M, Fuksiewicz M, Michalski W, Chechlinska M (2005) Clinical significance of serum cytokine measurements in untreated colorectal cancer patients: soluble tumor necrosis factor receptor type I—an independent prognostic factor. Tumour Biol 26:186–194CrossRefPubMed

24.

Esfandi F, Mohammadzadeh Ghobadloo S, Basati G (2006) Interleukin-6 level in patients with colorectal cancer. Cancer Lett 244:76–78CrossRefPubMed

25.

Belluco C, Nitti D, Frantz M, Toppan P, Basso D, Plebani M, Lise M, Jessup JM (2000) Interleukin-6 blood level is associated with circulating carcinoembryonic antigen and prognosis in patients with colorectal cancer. Ann Surg Oncol 7:133–138CrossRefPubMed

26.

Kaminska J, Kowalska MM, Nowacki MP, Chwalinski MG, Rysinska A, Fuksiewicz M (2000) CRP, TNF-alpha, IL-1ra, IL-6, IL-8 and IL-10 in blood serum of colorectal cancer patients. Pathol Oncol Res 6:38–41CrossRefPubMed

27.

Rich T, Innominato PF, Boerner J, Mormont MC, Iacobelli S, Baron B, Jasmin C, Levi F (2005) Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and dampened 24-hour rest-activity patterns in patients with metastatic colorectal cancer. Clin Cancer Res 11:1757–1764CrossRefPubMed

28.

Knupfer H, Preiss R (2007) Significance of interleukin-6 (IL-6) in breast cancer (review). Breast Cancer Res Treat 102:129–135CrossRefPubMed

29.

Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102:1369–1376CrossRefPubMed

30.

Hefler LA, Grimm C, Ackermann S, Malur S, Radjabi-Rahat AR, Leodolter S, Beckmann MW, Zeillinger R, Koelbl H, Tempfer CB (2003) An interleukin-6 gene promoter polymorphism influences the biological phenotype of ovarian cancer. Cancer Res 63:3066–3068PubMed

31.

Belluco C, Olivieri F, Bonafè M, Giovagnetti S, Mammano E, Scalerta R, Ambrosi A, Franceschi C, Nitti D, Lise M (2003) 174 G>C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in patients with colorectal cancer. Clin Cancer Res 9:2173–2176PubMed

32.

Tchirkov A, Khalil T, Chautard E, Mokhtari K, Véronèse L, Irthum B, Vago P, Kémény JL, Verrelle P (2007) Interleukin-6 gene amplification and shortened survival in glioblastoma patients. Br J Cancer 96:474–476CrossRefPubMed

Title: Serum interleukin-6 levels in colorectal cancer patients—a summary of published results
Authors: Heike Knüpfer
Rainer Preiss
Publication date: 01-02-2010
Publisher: Springer-Verlag
Published in: International Journal of Colorectal Disease / Issue 2/2010
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-009-0818-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Serum interleukin-6 levels in colorectal cancer patients—a summary of published results

Abstract

Introduction

Materials and methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Materials and methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2010

Extended lymph node dissection in colorectal cancer surgery. Reliability and reproducibility in assessments of operative reports

Association of polymorphisms MTHFR C677T and A1298C with risk of colorectal cancer, genetic and epigenetic characteristic of tumors, and response to chemotherapy

Differential effects of NOD2 polymorphisms on colorectal cancer risk: a meta-analysis

Anal physiology testing in fecal incontinence: is it of any value?

Krukenberg tumors of colorectal origin: a dismal outcome—experience of a tertiary center

Proctitis due to retained staples after stapler hemorrhoidopexy and a review of literature