Vol 7, No 2 (2018)
Research paper
Published online: 2018-04-04

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The levels of interleukin-2 and interleukin-10 in patients with type 2 diabetes and colon cancer

Irina Bosek1, Roman Kuczerowski1, Tomasz Miłek2, Michał Rabijewski1, Beata Kaleta3, Monika Kniotek3, Piotr Ciostek2, Paweł Piątkiewicz1
Clin Diabetol 2018;7(2):114-121.

Abstract

Introduction. The risk of colon cancer (CC) develop­ment is increased significantly among patients with type 2 diabetes (T2DM). A mechanism responsible for a higher prevalence of CC among diabetic patients may be associated with disturbances of the immune system. Cytokines — interleukin-2 (IL-2) and interleukin-10 (IL- -10) play relevant role in the immune response. The aim of this study was to investigate the differences in the immunological state in terms of IL-2 and IL-10 levels among groups of patients with T2DM, patients with CC, patients with T2DM and CC and patients without these diseases.

Material and methods. 80 patients were included in the tests and split into 4 groups: group 1 — 24 patients with T2DM, group 2 — 24 patients with CC, group 3 — 10 patients with CC and T2DM, and group 4 — 22 persons without T2DM or CC. Colonoscopy was per­formed for all the patients. All cases of colon cancer were confirmed by histopathological examination. Laboratory measurements included blood tests such as fasting glucose, insulin, C-peptide and HbA1c. The serum concentration of IL-2 and IL-10 was determined by the immunoenzymatic (ELISA) method.

Results. The concentration of IL-2 was statistically higher in the group of patients with T2DM and CC than in the groups of patients without those diseases (4.21 ± 1.61 SE pg/ml vs. group 1 — 1.57 ± 0.44 SE pg/ /ml, group 2 — 1.64 ± 0.27 SE pg/ml, group 4 — 1.95 ± 0.47 SE pg/ml; p < 0.05). There were no statistically significant differences in the concentrations of IL-10 in patients with T2DM and CC compared with other subjects. The level of fasting glucose and HbA1c in the groups of patients with T2DM (group 1) and T2DM with CC (group 3) was statistically higher than in the groups of patients without T2DM. There were no statistically significant differences between the groups in levels of insulin, C-peptide and HOMA-IR.

Conclusions. The concentration of IL-2 was statistically higher in the group of patients with T2DM and colon cancer than in other groups. Elevated level of IL-2 can be a marker of an increased risk of CC in people with type 2 diabetes. It might be useful in indicating a group of patients with differences in immune system particularly susceptible to the development of colon cancer.  

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References

  1. International Agency for Research on Cancer: GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Lyon, International Agency for Research on Cancer. ; 2014.
  2. Bray F, Jemal A, Grey N, et al. Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol. 2012; 13(8): 790–801.
  3. Larsson SC, Orsini N, Wolk A. Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst. 2005; 97(22): 1679–1687.
  4. González N, Prieto I, Del Puerto-Nevado L, et al. DiabetesCancerConnect Consortium. 2017 update on the relationship between diabetes and colorectal cancer: epidemiology, potential molecular mechanisms and therapeutic implications. Oncotarget. 2017; 8(11): 18456–18485.
  5. He J, Stram DO, Kolonel LN, et al. The association of diabetes with colorectal cancer risk: the Multiethnic Cohort. Br J Cancer. 2010; 103(1): 120–126.
  6. Rutkowski M, Bandosz P, Czupryniak L, et al. Prevalence of diabetes and impaired fasting glucose in Poland--the NATPOL 2011 Study. Diabet Med. 2014; 31(12): 1568–1571.
  7. Li Y, Wang L, Pappan L, et al. IL-1β promotes stemness and invasiveness of colon cancer cells through Zeb1 activation. Mol Cancer. 2012; 11: 87.
  8. Lin YC, Mahalingam J, Chiang JM, et al. Activated but not resting regulatory T cells accumulated in tumor microenvironment and correlated with tumor progression in patients with colorectal cancer. Int J Cancer. 2013; 132(6): 1341–1350.
  9. Svensson H, Olofsson V, Lundin S, et al. Accumulation of CCR4⁺CTLA-4 FOXP3⁺CD25(hi) regulatory T cells in colon adenocarcinomas correlate to reduced activation of conventional T cells. PLoS One. 2012; 7(2): e30695.
  10. Waldner MJ, Foersch S, Neurath MF. Interleukin-6--a key regulator of colorectal cancer development. Int J Biol Sci. 2012; 8(9): 1248–1253.
  11. Ng TH, Britton GJ, Hill EV, et al. Regulation of adaptive immunity; the role of interleukin-10. Front Immunol. 2013; 4: 129.
  12. Wu D, Wu P, Huang Qi, et al. Interleukin-17: a promoter in colorectal cancer progression. Clin Dev Immunol. 2013; 2013: 436307.
  13. Zhang J, Mao T, Wang S, et al. Interleukin-35 expression is associated with colon cancer progression. Oncotarget. 2017; 8(42): 71563–71573.
  14. Malek TR. The biology of interleukin-2. Annu Rev Immunol. 2008; 26: 453–479.
  15. Francisco CO, Catai AM, Moura-Tonello SCG, et al. Cytokine profile and lymphocyte subsets in type 2 diabetes. Braz J Med Biol Res. 2016; 49(4): e5062.
  16. Yuhara H, Steinmaus C, Cohen SE, et al. Is diabetes mellitus an independent risk factor for colon cancer and rectal cancer? Am J Gastroenterol. 2011; 106(11): 1911–21; quiz 1922.
  17. Boyman O, Sprent J. The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol. 2012; 12(3): 180–190.
  18. Mannino MH, Zhu Z, Xiao H, et al. The paradoxical role of IL-10 in immunity and cancer. Cancer Lett. 2015; 367(2): 103–107.
  19. Mosser DM, Zhang X. Interleukin-10: new perspectives on an old cytokine. Immunol Rev. 2008; 226: 205–218.
  20. Saraiva M, O'Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol. 2010; 10(3): 170–181.
  21. Mager LF, Wasmer MH, Rau TT, et al. Cytokine-Induced Modulation of Colorectal Cancer. Front Oncol. 2016; 6: 96.
  22. Sato T, Terai M, Tamura Y, et al. Interleukin 10 in the tumor microenvironment: a target for anticancer immunotherapy. Immunol Res. 2011; 51(2-3): 170–182.
  23. Hsieh MC, Lee TC, Cheng SM, et al. The influence of type 2 diabetes and glucose-lowering therapies on cancer risk in the Taiwanese. Exp Diabetes Res. 2012; 2012: 413782.
  24. De Bruijn KMJ, Arends LR, Hansen BE, et al. Systematic review and meta-analysis of the association between diabetes mellitus and incidence and mortality in breast and colorectal cancer. Br J Surg. 2013; 100(11): 1421–1429.
  25. Giovaucci E. Metabolic syndrome, hiperinsulinemia and colon cancer: a review. Am J Clin Nutr. 2007; 86(3): 836–842.
  26. Piątkiewicz P, Czech A. Glucose metabolism disorders and the risk of cancer. Arch Immunol Ther Exp (Warsz). 2011; 59(3): 215–230.
  27. Jenab M, Riboli E, Cleveland RJ, et al. Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2007; 121(2): 368–376.
  28. Holden SE. Diabetes and Cancer. Endocr Dev. 2016; 31: 135–145.
  29. Brunner EJ, Kivimäki M, Witte DR, et al. Inflammation, insulin resistance, and diabetes--Mendelian randomization using CRP haplotypes points upstream. PLoS Med. 2008; 5(8): e155.
  30. Yaturu S, Rains J, Jain SK. Relationship of elevated osteoprotegerin with insulin resistance, CRP, and TNF-alpha levels in men with type 2 diabetes. Cytokine. 2008; 44(1): 168–171.
  31. Schloot NC, Hanifi-Moghaddam P, Goebel C, et al. Serum IFN-gamma and IL-10 levels are associated with disease progression in non-obese diabetic mice. Diabetes Metab Res Rev. 2002; 18(1): 64–70.
  32. Kim S, Keku TO, Martin C, et al. Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res. 2008; 68(1): 323–328.
  33. Sasaki Yu, Takeda H, Sato T, et al. Serum Interleukin-6, insulin, and HOMA-IR in male individuals with colorectal adenoma. Clin Cancer Res. 2012; 18(2): 392–399.
  34. Day SD, Enos RT, McClellan JL, et al. Linking inflammation to tumorigenesis in a mouse model of high-fat-diet-enhanced colon cancer. Cytokine. 2013; 64(1): 454–462.
  35. Zhu M, Zhu Y, Lance P. TNFα-activated stromal COX-2 signalling promotes proliferative and invasive potential of colon cancer epithelial cells. Cell Prolif. 2013; 46(4): 374–381.
  36. Putoczki TL, Thiem S, Loving A, et al. Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. Cancer Cell. 2013; 24(2): 257–271.
  37. Prieto-Hontoria PL, Pérez-Matute P, Fernández-Galilea M, et al. Role of obesity-associated dysfunctional adipose tissue in cancer: a molecular nutrition approach. Biochim Biophys Acta. 2011; 1807(6): 664–678.
  38. Gallagher EJ, LeRoith D. Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality. Physiol Rev. 2015; 95(3): 727–748.
  39. Marszałek A, Szylberg L, Wiśniewska E, et al. Impact of COX-2, IL-1β, TNF-α, IL-4 and IL-10 on the process of carcinogenesis in the large bowel. Pol J Pathol. 2012; 63(4): 221–227.
  40. Setia S, Nehru B, Sanyal SN. Activation of NF-κB: bridging the gap between inflammation and cancer in colitis-mediated colon carcinogenesis. Biomed Pharmacother. 2014; 68(1): 119–128.
  41. Klampfer L. Cytokines, Inflammation and Colon Cancer. Current Cancer Drug Targets. 2011; 11(4): 451–464.
  42. Kalvakolanu DV. Cytokine signaling in cancer: Novel players and pathways. Cytokine. 2017; 89: 1–3.
  43. Abtahi S, Davani F, Mojtahedi Z, et al. Dual association of serum interleukin-10 levels with colorectal cancer. J Cancer Res Ther. 2017; 13(2): 252–256.
  44. Malek TR, Castro I. Interleukin-2 receptor signaling: at the interface between tolerance and immunity. Immunity. 2010; 33(2): 153–165.
  45. Lin YC, Mahalingam J, Chiang JM, et al. Activated but not resting regulatory T cells accumulated in tumor microenvironment and correlated with tumor progression in patients with colorectal cancer. Int J Cancer. 2013; 132(6): 1341–1350.
  46. Kang T, Mao CP, He L, et al. Tumor-Targeted Delivery of IL-2 by NKG2D Leads to Accumulation of Antigen-Specific CD8+ T Cells in the Tumor Loci and Enhanced Anti-Tumor Effects. PLoS ONE. 2012; 7(4): e35141.
  47. Djaldetti M, Bessler H. Modulators affecting the immune dialogue between human immune and colon cancer cells. World J Gastrointest Oncol. 2014; 6(5): 129–138.
  48. Commins S, Steinke JW, Borish L. The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29. J Allergy Clin Immunol. 2008; 121(5): 1108–1111.