Top

BMC Gastroenterology

Published in:

Open Access 01-12-2015 | Research article

Changes of cytokine levels in a mouse model of post-infectious irritable bowel syndrome

Authors: Bo Yang, Xuchun Zhou, Cheng Lan

Published in: BMC Gastroenterology | Issue 1/2015

Abstract

Background

Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder. Post-infectious IBS (PI-IBS) is caused by an acute gastrointestinal infection preceding the onset of symptoms. However, the pathophysiology of PI-IBS is not clear, and the purpose of this study was to investigate the probable immune mechanisms of PI-IBS.

Methods

C57BL/6 mice were randomly assigned to either an infection group or a control group. Mice in the infection group were infected with Trichinella spiralis to establish a model of PI-IBS (500 Trichinella), while control mice received only salt solution. Visceral sensitivity of colorectal distention in mice was evaluated by abdominal withdrawal reflex scores and intestinal inflammation was assessed using hematoxylin-eosin staining; at day 56 post-infection, the mRNA and protein levels of specific cytokines in the gut segments were detected using reverse-transcription polymerase chain reaction and enzyme-linked immunoabsorbent assay.

Results

Levels of interferon γ and interleukin (IL)-17 in the PI-IBS group were significantly increased in the duodenum and ileum, and IL-10 was decreased in the jejunum, ileum, and colon compared with control mice. However, the expression level of IL-1β was not significantly different between the two groups.

Conclusions

The present study suggests that the local low-grade inflammation and immune activation that are an important component of the pathophysiology of PI-IBS are primarily induced and maintained by specific cytokines.

Choung RS, Locke III GR. Epidemiology of IBS. Gastroenterol Clin N Am. 2011;40(1):1–10.CrossRef

Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130(5):1480–91.PubMedCrossRef

Qin H-Y, Wu JY, Tong X-D, Sung JY, Xu H-X, Bian Z-X. Systematic review of animal models of post-infectious/post-inflammatory irritable bowel syndrome. J Gastroenterol. 2011;46(2):164–74.PubMedCrossRef

Bercik P, Wang L, Verdu EF, Mao YK, Blennerhassett P, Khan WI, et al. Visceral hyperalgesia and intestinal dysmotility in a mouse model of postinfective gut dysfunction. Gastroenterology. 2004;127(1):179–87.PubMedCrossRef

Long Y, Wang W, Wang H, Hao L, Qian W, Hou X. Characteristics of intestinal lamina propria dendritic cells in a mouse model of postinfectious irritable bowel syndrome. J Gastroenterol Hepatol. 2012;27(5):935–44.PubMedCrossRef

Spiller R, Garsed K. Postinfectious irritable bowel syndrome. Gastroenterology. 2009;136(6):1979–88.PubMedCrossRef

Elsenbruch S, Holtmann G, Oezcan D, Lysson A, Janssen O, Goebel MU, et al. Are there alterations of neuroendocrine and cellular immune responses to nutrients in women with irritable bowel syndrome [quest]. Am J Gastroenterol. 2004;99(4):703–10.PubMedCrossRef

Liebregts T, Adam B, Bredack C, Röth A, Heinzel S, Lester S, et al. Immune activation in patients with irritable bowel syndrome. Gastroenterology. 2007;132(3):913–20.PubMedCrossRef

Spiller RC, Jenkins D, Thornley JP, Hebden JM, Wright T, Skinner M, et al. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acuteCampylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut. 2000;47(6):804–11.PubMedPubMedCentralCrossRef

10.

Chadwick VS, Chen W, Shu D, Paulus B, Bethwaite P, Tie A, et al. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology. 2002;122(7):1778–83.PubMedCrossRef

11.

Wheatcroft J, Wakelin D, Smith A, Mahoney CR, Mawe G, Spiller R. Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunction. Neurogastroenterol Motil. 2005;17(6):863–70.PubMedCrossRef

12.

Al-Khatib K, Lin HC. Immune activation and gut microbes in irritable bowel syndrome. Gut Liver. 2009;3(1):14–9.PubMedPubMedCentralCrossRef

13.

Buhner S, Li Q, Vignali S, Barbara G, De Giorgio R, Stanghellini V, et al. Activation of human enteric neurons by supernatants of colonic biopsy specimens from patients with irritable bowel syndrome. Gastroenterology. 2009;137(4):1425–34.PubMedCrossRef

14.

Park JH, Rhee PL, Kim HS, Lee JH, Kim YH, Kim JJ, et al. Mucosal mast cell counts correlate with visceral hypersensitivity in patients with diarrhea predominant irritable bowel syndrome. J Gastroenterol Hepatol. 2006;21(1 Pt 1):71–8.PubMedCrossRef

15.

Barbara G, Wang B, Stanghellini V, de Giorgio R, Cremon C, Di Nardo G, et al. Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology. 2007;132(1):26–37.PubMedCrossRef

16.

Kalia N, Hardcastle J, Keating C, Grasa L, Pelegrin P, Bardhan KD, et al. Intestinal secretory and absorptive function in Trichinella spiralis mouse model of postinfective gut dysfunction: role of bile acids. Gut. 2008;57(1):41–9.PubMedCrossRef

17.

Barbara G, Vallance BA, Collins SM. Persistent intestinal neuromuscular dysfunction after acute nematode infection in mice. Gastroenterology. 1997;113(4):1224–32.PubMedCrossRef

18.

Tanovic A, Fernandez E, Jimenez M. Alterations in intestinal contractility during inflammation are caused by both smooth muscle damage and specific receptor-mediated mechanisms. Croat Med J. 2006;47(2):318–26.PubMedPubMedCentral

19.

Torrents D, Vergara P. In vivo changes in the intestinal reflexes and the response to CCK in the inflamed small intestine of the rat. Am J Physiol Gastrointest Liver Physiol. 2000;279(3):G543–51.PubMed

20.

Bashashati M, Rezaei N, Andrews CN, Chen C-Q, Daryani NE, Sharkey KA, et al. Cytokines and irritable bowel syndrome: where do we stand? Cytokine. 2012;57(2):201–9.PubMedCrossRef

21.

Tjwa ET, Bradley JM, Keenan CM, Kroese A, Sharkey KA. Interleukin-1β activates specific populations of enteric neurons and enteric glia in the guinea pig ileum and colon. Am J Physiol Gastrointest Liver Physiol. 2003;285(6):G1268–76.PubMedCrossRef

22.

Kelles A, Janssens J, Tack J. IL‐1β and IL‐6 excite neurones and suppress cholinergic neurotransmission in the myenteric plexus of the guinea pig. Neurogastroenterol Motil. 2000;12(6):531–8.PubMedCrossRef

23.

Fargeas M-J, Fioramonti J, Bueno L. Central action of interleukin 1 on intestinal motility in rats: mediation by Two mechanisms. Gastroenterology-Baltimore then Philadelphia. 1993;104:377–7.

24.

Shen L, Su L, Turner JR. Mechanisms and functional implications of intestinal barrier defects. Dig Dis. 2009;27(4):443–9.PubMedPubMedCentralCrossRef

25.

Ferrier L, Mazelin L, Cenac N, Desreumaux P, Janin A, Emilie D, et al. Stress-induced disruption of colonic epithelial barrier: role of interferon-γ and myosin light chain kinase in mice. Gastroenterology. 2003;125(3):795–804.PubMedCrossRef

26.

Han X, Fink MP, Delude RL. Proinflammatory cytokines cause no [middle dot]-dependent and -independent changes in expression and localization of tight junction proteins in intestinal epithelial cells. Shock. 2003;19(3):229–37.PubMedCrossRef

27.

Gasche C, Bakos S, Dejaco C, Tillinger W, Zakeri S, Reinisch W. IL-10 secretion and sensitivity in normal human intestine and inflammatory bowel disease. J Clin Immunol. 2000;20(5):362–70.PubMedCrossRef

28.

Andoh A, Takaya H, Makino J, Sato H, Bamba S, Araki Y, et al. Cooperation of interleukin-17 and interferon-γ on chemokine secretion in human fetal intestinal epithelial cells. Clin Exp Immunol. 2001;125(1):56–63.PubMedPubMedCentralCrossRef

29.

La J-H, Kim T-W, Sung T-S, Kang J-W, Kim H-J, Yang I-S. Visceral hypersensitivity and altered colonic motility after subsidence of inflammation in a rat model of colitis. World J Gastroenterol. 2003;9(12):2791–5.PubMedPubMedCentralCrossRef

30.

Al-Chaer ED, Kawasaki M, Pasricha PJ. A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development. Gastroenterology. 2000;119(5):1276–85.PubMedCrossRef

31.

Dieleman LA, Palmen MJ, Akol H, Bloemena E, Peña AS, Meuwissen SG, et al. Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol. 1998;114(3):385–91.PubMedPubMedCentralCrossRef

32.

Micili SC, Goker A, Sayin O, Akokay P, Ergur BU. The effect of lipoic acid on wound healing in a full thickness uterine injury model in rats. J Mol Histol 2013;44(3):339-45.

33.

Ishihara S, Tada Y, Fukuba N, Oka A, Kusunoki R, Mishima Y, et al. Pathogenesis of irritable bowel syndrome–review regarding associated infection and immune activation. Digestion. 2013;87(3):204–11.PubMedCrossRef

34.

Sengupta JN, Saha JK, Goyal RK. Stimulus–response function studies of esophageal mechanosensitive nociceptors in sympathetic afferents of opossum. J Neurophysiol. 1990;64(3):796–812.PubMed

35.

Spiller RC. Postinfectious irritable bowel syndrome. Gastroenterology. 2003;124(6):1662–71.PubMedCrossRef

36.

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(3):97–105.PubMedPubMedCentralCrossRef

37.

Cremon C, Gargano L, Morselli-Labate AM, Santini D, Cogliandro RF, De Giorgio R, et al. Mucosal immune activation in irritable bowel syndrome: gender-dependence and association with digestive symptoms. Am J Gastroenterol. 2009;104(2):392–400.PubMedCrossRef

38.

Ford AC, Talley NJ. Mucosal inflammation as a potential etiological factor in irritable bowel syndrome: a systematic review. J Gastroenterol. 2011;46(4):421–31.PubMedCrossRef

39.

Corinaldesi R, Stanghellini V, Cremon C, Gargano L, Cogliandro RF, De Giorgio R, et al. Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof-of-concept study. Aliment Pharmacol Ther. 2009;30(3):245–52.PubMedCrossRef

40.

Feng B, La JH, Schwartz ES, Gebhart GF. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Neural and neuro-immune mechanisms of visceral hypersensitivity in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2012;302(10):8.CrossRef

41.

Törnblom H, Lindberg G, Nyberg B, Veress B. Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome. Gastroenterology. 2002;123(6):1972–9.PubMedCrossRef

42.

Li L, Huang L, Vergis AL, Ye H, Bajwa A, Narayan V, et al. IL-17 produced by neutrophils regulates IFN-γ–mediated neutrophil migration in mouse kidney ischemia-reperfusion injury. J Clin Invest. 2010;120(1):331.PubMedCrossRef

43.

Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;201(2):233–40.PubMedPubMedCentralCrossRef

44.

Iwakura Y, Ishigame H, Saijo S, Nakae S. Functional Specialization of Interleukin-17 Family Members. Immunity. 2011;34(2):149–62.PubMedCrossRef

45.

Chomarat P, Rissoan MC, Banchereau J, Miossec P. Interferon gamma inhibits interleukin 10 production by monocytes. J Exp Med. 1993;177(2):523–7.PubMedCrossRef

46.

Raetz M, S-h H, Wilhelm CL, Kirkland D, Benson A, Sturge CR, et al. Parasite-induced TH1 cells and intestinal dysbiosis cooperate in IFN-[gamma]-dependent elimination of Paneth cells. Nat Immunol. 2013;14(2):136–42.PubMedCrossRef

47.

Capaldo CT, Beeman N, Hilgarth RS, Nava P, Louis NA, Naschberger E, et al. IFN-[gamma] and TNF-[alpha]-induced GBP-1 inhibits epithelial cell proliferation through suppression of [beta]-catenin/TCF signaling. Mucosal Immunol. 2012;5(6):681–90.PubMedPubMedCentralCrossRef

48.

Scharl M, Paul G, Barrett KE, McCole DF. AMP-activated Protein Kinase Mediates the Interferon-{gamma}-induced Decrease in Intestinal Epithelial Barrier Function. J Biol Chem. 2009;284(41):27952–63.PubMedPubMedCentralCrossRef

49.

Zhu S, Qian Y. IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential. Clin Sci. 2012;122(11):487–511.PubMedCrossRef

50.

Costa VS, Mattana TCC, da Silva MER. Unregulated IL-23/IL-17 immune response in autoimmune diseases. Diabetes Res Clin Pract. 2010;88(3):222–6.PubMedCrossRef

51.

Fossiez F, Djossou O, Chomarat P, Flores-Romo L, Ait-Yahia S, Maat C, et al. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med. 1996;183(6):2593–603.PubMedCrossRef

52.

Sabat R, Grütz G, Warszawska K, Kirsch S, Witte E, Wolk K, et al. Biology of interleukin-10. Cytokine Growth Factor Rev. 2010;21(5):331–44.PubMedCrossRef

53.

Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O’Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991;147(11):3815–22.PubMed

54.

D’Andrea A, Aste-Amezaga M, Valiante NM, Ma X, Kubin M, Trinchieri G. Interleukin 10 (IL-10) inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. J Exp Med. 1993;178(3):1041–8.PubMedCrossRef

55.

de Waal Malefyt R, Haanen J, Spits H, Roncarolo MG, te Velde A, Figdor C, et al. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med. 1991;174(4):915–24.PubMedCrossRef

56.

Willems F, Marchant A, Delville J-P, Gérard C, Delvaux A, Velu T, et al. Interleukin-10 inhibits B7 and intercellular adhesion molecule-1 expression on human monocytes. Eur J Immunol. 1994;24(4):1007–9.PubMedCrossRef

57.

Speiran K, Bailey DP, Fernando J, Macey M, Barnstein B, Kolawole M, et al. Endogenous suppression of mast cell development and survival by IL-4 and IL-10. J Leukoc Biol. 2009;85(5):826–36.PubMedPubMedCentralCrossRef

58.

Groschwitz KR, Ahrens R, Osterfeld H, Gurish MF, Han X, Åbrink M, et al. Mast cells regulate homeostatic intestinal epithelial migration and barrier function by a chymase/Mcpt4-dependent mechanism. Proc Natl Acad Sci. 2009;106(52):22381–6.PubMedPubMedCentralCrossRef

59.

Al-Sadi R, Guo S, Ye D, Ma TY. TNF-α modulation of intestinal epithelial tight junction barrier is regulated by ERK1/2 activation of Elk-1. Am J Pathol. 2013;183(6):1871–84.PubMedCrossRef

Title: Changes of cytokine levels in a mouse model of post-infectious irritable bowel syndrome
Authors: Bo Yang
Xuchun Zhou
Cheng Lan
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: BMC Gastroenterology / Issue 1/2015
Electronic ISSN: 1471-230X
DOI: https://doi.org/10.1186/s12876-015-0272-8

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Changes of cytokine levels in a mouse model of post-infectious irritable bowel syndrome

Abstract

Background

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2015

Characteristics and factors related to quality of life in Mexican Mestizo patients with celiac disease

Rare cause of severe anemia due to pyogenic granuloma in the jejunum

Helicobacter pylori infection is not associated with fatty liver disease including non-alcoholic fatty liver disease: a large-scale cross-sectional study in Japan

Video capsule endoscopy as the initial examination for overt obscure gastrointestinal bleeding can efficiently identify patients who require double-balloon enteroscopy

The relationship between irritable bowel syndrome, functional dyspepsia, chronic fatigue and overactive bladder syndrome: a controlled study 6 years after acute gastrointestinal infection

Factors impacting physicians’ decisions to prevent variceal hemorrhage

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page