Intest Res.  2020 Jan;18(1):115-120. 10.5217/ir.2019.00125.

Proinflammatory cytokines in irritable bowel syndrome: a comparison with inflammatory bowel disease

• Mitselou A
• Grammeniatis V
• Varouktsi
• Papadatos
• Katsanos K
• Galani V

• KMID: 2501373
• DOI: http://doi.org/10.5217/ir.2019.00125

Abstract

Background/Aims
Irritable bowel syndrome (IBS) is a common disease often considered as a functional intestinal disorder. Inflammation in IBS is a quite intriguing theory. The aim of this study was to investigate tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 expression in inflammatory bowel disease (IBD) patients, IBS patients and normal controls.
Methods
IBS and IBD patients along with normal controls were recruited in the study. In all groups, 2 pinch biopsies were taken at each of 3 anatomical sites (terminal ileum, cecum, and rectum). IBS patients were also subcategorized according to the syndrome clinical manifestations. Two monoclonal antibodies (mAb), TNF-α mAb and IL-6 mAb, and one polyclonal antibody IL-1β mAb were applied for immunohistochemical analysis.
Results
In IBD patients intensity of TNF-α and IL-1β were lower than in IBS patients or controls, while IL-6 was significantly increased comparing to the aforementioned groups. In IBS patients TNF-α was increased comparing to IBD patients or controls, while IL-6 and IL-1β were similar to controls. In IBS subgroups, TNF-α was lower in diarrhea predominant IBS patients and higher constipation predominant IBS patients. Differences among IBS subgroups regarding IL-6 and IL-1β were nonsignificant.
Conclusions
IL-6 seems to be the most important proinflammatory cytokine in IBD patients, while TNF-α could play a more significant role in IBS pathogenesis.

Keyword

Proinflammatory cytokines; Irritable bowel syndrome; Inflammatory bowel disease

Reference

1. Chadwick VS, Chen W, Shu D, et al. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology. 2002; 122:1778–1783.

2. Oberndorff-Klein Woolthuis AH, Brummer RJ, de Wit NJ, Muris JW, Stockbrügger RW. Irritable bowel syndrome in general practice: an overview. Scand J Gastroenterol Suppl. 2004; (241):17–22.

3. Drossman DA, Camilleri M, Mayer EA, Whitehead WE. AGA technical review on irritable bowel syndrome. Gastroenterology. 2002; 123:2108–2131.

4. Cayley WE Jr. Irritable bowel syndrome. BMJ. 2005; 330:632.

5. Spiller RC. Irritable bowel syndrome. Br Med Bull. 2005; 72:15–29.

6. Ohman L, Simrén M. Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nat Rev Gastroenterol Hepatol. 2010; 7:163–173.

7. Akiho H, Ihara E, Nakamura K. Low-grade inflammation plays a pivotal role in gastrointestinal dysfunction in irritable bowel syndrome. World J Gastrointest Pathophysiol. 2010; 1:97–105.

8. Travis SP, Schnell D, Krzeski P, et al. Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Gut. 2012; 61:535–542.

9. Papadakis KA, Targan SR. Role of cytokines in the pathogenesis of inflammatory bowel disease. Annu Rev Med. 2000; 51:289–298.

10. Galani V, Constantopoulos S, Manda-Stachouli C, et al. Additional proteins in BAL fluid of Metsovites environmentally exposed to asbestos: more evidence of “protection” against neoplasia? Chest. 2002; 121:273–278.

11. Wang L, Walia B, Evans J, Gewirtz AT, Merlin D, Sitaraman SV. IL-6 induces NF-kappa B activation in the intestinal epithelia. J Immunol. 2003; 171:3194–3201.

12. Sanchez-Munoz F, Dominguez-Lopez A, Yamamoto-Furusho JK. Role of cytokines in inflammatory bowel disease. World J Gastroenterol. 2008; 14:4280–4288.

13. Mudter J, Neurath MF. Apoptosis of T cells and the control of inflammatory bowel disease: therapeutic implications. Gut. 2007; 56:293–303.

14. Kallen KJ. The role of transsignalling via the agonistic soluble IL-6 receptor in human diseases. Biochim Biophys Acta. 2002; 1592:323–343.

15. Rose-John S, Scheller J, Elson G, Jones SA. Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. J Leukoc Biol. 2006; 80:227–236.

16. Kastamoulas M, Chondrogiannis G, Kanavaros P, et al. Cytokine effects on cell survival and death of A549 lung carcinoma cells. Cytokine. 2013; 61:816–825.

17. Chondrogiannis G, Kastamoulas M, Kanavaros P, et al. Cytokine effects on cell viability and death of prostate carcinoma cells. Biomed Res Int. 2014; 2014:536049.

18. Galani V, Kastamoulas M, Varouktsi A, Lampri E, Mitselou A, Arvanitis DL. IFNs-signaling effects on lung cancer: an up-todate pathways-specific review. Clin Exp Med. 2017; 17:281–289.

19. Scaldaferri F, Correale C, Gasbarrini A, Danese S. Mucosal biomarkers in inflammatory bowel disease: key pathogenic players or disease predictors? World J Gastroenterol. 2010; 16:2616–2625.

20. Martinsen TC, Herter R, Dybdahl JH, Waldum HL. Use of TNFalpha antibodies in treatment of inflammatory bowel disease. Tidsskr Nor Laegeforen. 2010; 130:273–277.

21. Maeda M, Watanabe N, Neda H, et al. Serum tumor necrosis factor activity in inflammatory bowel disease. Immunopharmacol Immunotoxicol. 1992; 14:451–461.

22. Andus T, Targan SR, Deem R, Toyoda H. Measurement of tumor necrosis factor alpha mRNA in small numbers of cells by quantitative polymerase chain reaction. Reg Immunol. 1993; 5:11–17.

23. Youngman KR, Simon PL, West GA, et al. Localization of intestinal interleukin 1 activity and protein and gene expression to lamina propria cells. Gastroenterology. 1993; 104:749–758.

24. Oliva-Hemker M, Fiocchi C. Etiopathogenesis of inflammatory bowel disease: the importance of the pediatric perspective. Inflamm Bowel Dis. 2002; 8:112–128.

25. Ruffolo C, Scarpa M, Faggian D, et al. Cytokine network in rectal mucosa in perianal Crohn’s disease: relations with inflammatory parameters and need for surgery. Inflamm Bowel Dis. 2008; 14:1406–1412.

26. Fiocchi C. What is “physiological” intestinal inflammation and how does it differ from “pathological” inflammation? Inflamm Bowel Dis. 2008; 14 Suppl 2:S77–S78.

27. Monteleone I, Pallone F, Monteleone G. Interleukin-23 and Th17 cells in the control of gut inflammation. Mediators Inflamm. 2009; 2009:297645.