Diagnosis and management of inflammatory bowel disease in childrenBMJ 2017; 357 doi: https://doi.org/10.1136/bmj.j2083 (Published 31 May 2017) Cite this as: BMJ 2017;357:j2083
All rapid responses
Interleukin-10 in IBD and colon cancer--A major break through. Re: Diagnosis and management of inflammatory bowel disease in children
The insightful and informative clinical review on inflammatory bowel disease in children, as presented by Stephanie B Oliveira and Iona M Monteiro  has been applauded by many paediatricians and physicians.
Inflammatory bowel disease (IBD) is an umbrella term mainly used to describe two lifetime disorders: ulcerative colitis and Crohn's disease, while ulcerative colitis increases the risk of colon cancer. IBD can also affect other organs; for example, someone with IBD may have arthritis, skin conditions, inflammation of the eye, liver and kidney disorders, or bone loss .
Several studies showed that IBD and IBD related colon cancers involve different levels of immune regulation which need to be elucidated in this context.
Immuno-pathological basis of IBD:
Human intestinal lamina propria T lymphocytes (LPL-T) are constantly exposed to a large number of luminal antigens, yet generally systemic immune responses do not develop . The mechanisms underlying this particular type of unresponsiveness in the intestinal compartment involve different levels of immune regulation.
Interleukin (IL)-10 is an important immune-regulatory cytokine produced by many cell populations. Its main biological function seems to be the limitation and termination of inflammatory responses and the regulation of differentiation and proliferation of several immune cells such as T cells, B cells, natural killer cells, antigen-presenting cells, mast cells, and granulocytes, while Activated LPL-T releases relatively high amounts of IL-10 caused by increased sensitivity of LPL-T to CD2 co-stimulation.  Immune-modulation by cytokines could play a role in maintaining hypo-responsiveness in the gut which is supported by the finding that interleukin (IL) 10 and IL-2 knockout mice develop chronic enterocolitis  IL-10 down regulates gene expression and synthesis of inflammatory cytokines/chemokines, such as TNFα, IL-1, IL-6, IL-8  The characteristic immunological changes in chronic inflammatory bowel disease, such as enhanced mucosal IL-1β, IL-6, TNFα, and IFN-γ production could be explained by altered mucosal IL-10 homoeostasis .Intestinal epithelial cells are responsible for the basic IL-10 secretion involved in mediating permanent ‘immuno-unresponsiveness’ in the normal intestinal mucosa. In contrast to quiescent LPL-T, activated LPL-T release large amounts of IL-10, and when those cells are activated during inflammation , the principal task of IL-10 production by LPL-T is not in maintaining basic immunosuppression but in controlling inflammation in the gut, while CD2 provides a strong signal for proliferation and IL-10 secretion in LPL-T.
Role of IL-10 in colon cancer:
Chronic inflammation is closely linked to cancer [9, 10]. Cancer-related inflammation promotes the development and progression of tumor by different mechanisms, specifically by subverting immune response, inducing gene mutations, stimulating angiogenesis and cell proliferation and inhibiting apoptosis .IL–10 was generally known as an immunosuppressive cytokine which mainly promoted the proliferation and metastasis of tumor cells . However, IL–10 was newly found to active anti-tumor immunity in tumor microenvironment .An earlier study showed that Interleukin 10 (IL-10) selectively inhibits neovascularization in the Murine model  which may also play a role in tumor growth suppression. Significant restrain of colon tumors in mice was induced by delivery of anti-IL-10-receptor antibody in combination with CpG and CCL16, which supported the effectiveness of anti-IL–10 in anti-cancer therapy . In contrast, a recent study reported that recombined IL–10 induced tumor rejections by specifically targeting the tumor-infiltrating memory CD8+ T cells to activate the anti-tumor immune response .
In conclusion, IL–10 is a valuable biomarker for prognostic prediction and potential targeted treatment for IBD and colon cancer.
1. Diagnosis and management of inflammatory bowel disease in children
BMJ 2017; 357 doi: https://doi.org/10.1136/bmj.j2083 (Published 31 May 2017)
Cite this as: BMJ 2017; 357: j2083.
3. Braunsteina, J C, Qiaod L, F Autschbachb et al., Immunology:T cells of the human intestinal lamina propria are high producers of interleukin-10. Gut. 1997 Aug;41(2):215-20.
4. Asadullah K1, Sterry W, Volk HD.(2003) Interleukin-10 therapy--review of a new approach. Pharmacol Rev. 2003 Jun;55(2):241-69. PMID: 12773629 DOI: 10.1124/pr.55.2.4
5. Kühn R,Löhler J, Rennick D et al., (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75:263–274.
6. Axdorph U, Sjoberg J, Grimfors G, Landgren O, Porwit-MacDonald A, Bjorkholm M. Biological markers may add to prediction of outcome achieved by the International Prognostic Score in Hodgkin's disease. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO. 2000;11(11):1405–11. Epub 2001/01/06. . [PubMed]
7. Blay JY, Burdin N, Rousset F, Lenoir G, Biron P, Philip T, et al. Serum interleukin–10 in non-Hodgkin's lymphoma: a prognostic factor. Blood. 1993;82(7):2169–74. Epub 1993/10/01. . [PubMed]
8. Blay JY, Burdin N, Rousset F, Lenoir G, Biron P, Philip T, et al. Serum interleukin–10 in non-Hodgkin's lymphoma: a prognostic factor. Blood. 1993;82(7):2169–74. Epub 1993/10/01. . [PubMed]
9. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357(9255):539–45. doi: 10.1016/S0140-6736(00)04046-0 . [PubMed]
10. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–7. doi: 10.1038/nature01322 ; PubMed Central PMCID: PMC2803035. [PMC free article] [PubMed]
11. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44. doi: 10.1038/nature07205 . [PubMed]
12. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin–10 and the interleukin–10 receptor. Annual review of immunology. 2001;19:683–765. doi: 10.1146/annurev.immunol.19.1.683 . [PubMed]
13. Mumm JB, Oft M. Pegylated IL–10 induces cancer immunity: the surprising role of IL–10 as a potent inducer of IFN-gamma-mediated CD 8(+) T cell cytotoxicity. Bio Essays: news and reviews in molecular, cellular and developmental biology. 2013;35(7):623–31. Epub 2013/05/15. doi: 10.1002/bies.201300004 . [PubMed]
14. Solomon E. (2007) Interleukin 10 (IL-10) selectively inhibits neovascularization in the Murine model of Retinopathy of Prematurity. Thesis submitted to Florida Atlantic University, Florida.
15. Vicari AP, Chiodoni C, Vaure C, Ait-Yahia S, Dercamp C, Matsos F, et al. Reversal of tumor-induced dendritic cell paralysis by CpG immunostimulatory oligonucleotide and anti-interleukin 10 receptor antibody. The Journal of experimental medicine. 2002; 196(4):541–9. ; PubMed Central PMCID: PMC2196048. [PMC free article] [PubMed]
Competing interests: No competing interests
Very concise and informative article. Thanks to Oliveira and Monteiro.
However, I found a discepancy between the cover page title and the title inside the Journal of the 22 July. Title page says "How to diagnose IBS" in children but the inside article is "Diagnosis and management of inflammatory bowle disease in children". Is it a printing error or I am missing something here?
Thanks for clarification.
Competing interests: No competing interests