Gastroenterology
Volume 132, Issue 3 , Pages 913-920 , March 2007

Immune Activation in Patients With Irritable Bowel Syndrome

Presented in part at Digestive Disease Week 2006, Los Angeles, California, May 20-25, 2006.

  • Tobias Liebregts

      Affiliations

    • Department of Gastroenterology and Hepatology, University of Adelaide, Royal Adelaide Hospital, South Australia
    • Nerve-Gut Research Laboratory, Hanson Institute, Adelaide, SA, Australia
  • ,
  • Birgit Adam

      Affiliations

    • Department of Gastroenterology and Hepatology, University of Adelaide, Royal Adelaide Hospital, South Australia
    • Nerve-Gut Research Laboratory, Hanson Institute, Adelaide, SA, Australia
  • ,
  • Christoph Bredack

      Affiliations

    • Department of Gastroenterology and Hepatology, University of Adelaide, Royal Adelaide Hospital, South Australia
    • Nerve-Gut Research Laboratory, Hanson Institute, Adelaide, SA, Australia
  • ,
  • Alexander Röth

      Affiliations

    • Department of Internal Medicine, Division of Hematology, University of Essen, Germany
  • ,
  • Susanne Heinzel

      Affiliations

    • Department of Surgery, University of Adelaide, Royal Adelaide Hospital, South Australia
  • ,
  • Sue Lester

      Affiliations

    • Arthritis Research Laboratory, Hanson Institute, Adelaide, SA, Australia
  • ,
  • Sarah Downie–Doyle

      Affiliations

    • Arthritis Research Laboratory, Hanson Institute, Adelaide, SA, Australia
  • ,
  • Eric Smith

      Affiliations

    • Department of Surgery, University of Adelaide, Royal Adelaide Hospital, South Australia
  • ,
  • Paul Drew

      Affiliations

    • Department of Surgery, University of Adelaide, Royal Adelaide Hospital, South Australia
  • ,
  • Nicholas J. Talley

      Affiliations

    • Mayo Clinic, College of Medicine, Rochester, Minnesota
    • Department of Medicine, University of Sydney, New South Wales, Australia
  • ,
  • Gerald Holtmann

      Affiliations

    • Department of Gastroenterology and Hepatology, University of Adelaide, Royal Adelaide Hospital, South Australia
    • Nerve-Gut Research Laboratory, Hanson Institute, Adelaide, SA, Australia
    • Corresponding Author InformationAddress requests for reprints to: Gerald Holtmann, MD, FRACP, Professor of Medicine, Royal Adelaide Hospital, Department of Gastroenterology and Hepatology, University of Adelaide, North Terrace, Adelaide SA 5000, Australia. fax: (61) 8-8222-2414.

Received 5 April 2006 ,Accepted 7 December 2006.

References 

  1. Talley NJ, Spiller R. Irritable bowel syndrome: a little understood organic bowel disease?. Lancet. 2002;360:555–564
  2. McKendrick MW, Read NW. Irritable bowel syndrome—post salmonella infection. J Infect. 1994;29:1–3
  3. 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 acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut. 2000;47:804–811
  4. Adam B, Liebregts T, Gschossmann JM, Krippner C, Scholl F, Ruwe M, et al. Severity of mucosal inflammation as a predictor for alterations of visceral sensory function in a rat model. Pain. 2006;123:179–186
  5. van der Veek PP, van den BM, de Kroon YE, Verspaget HW, Masclee AA. Role of tumor necrosis factor-alpha and interleukin-10 gene polymorphisms in irritable bowel syndrome. Am J Gastroenterol. 2005;100:2510–2516
  6. Gonsalkorale WM, Perrey C, Pravica V, Whorwell PJ, Hutchinson IV. Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component?. Gut. 2003;52:91–93
  7. O’Mahony L, McCarthy J, Kelly P, Hurley G, Luo F, Chen K, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128:541–551
  8. Locke GR, Weaver AL, Melton LJ, Talley NJ. Psychosocial factors are linked to functional gastrointestinal disorders: a population based nested case-control study. Am J Gastroenterol. 2004;99:350–357
  9. Gwee KA, Graham JC, McKendrick MW, Collins SM, Marshall JS, Walters SJ, et al. Psychometric scores and persistence of irritable bowel after infectious diarrhoea. Lancet. 1996;347:150–153
  10. Simen BB, Duman CH, Simen AA, Duman RS. TNFalpha signaling in depression and anxiety: behavioral consequences of individual receptor targeting. Biol Psychiatry. 2006;59:775–785
  11. Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Muller-Lissner SA. Functional bowel disorders and functional abdominal pain. Gut. 1999;45(Suppl 2):II43–II47
  12. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67:361–370
  13. Holtmann G, Liebregts T, Siffert W. Molecular basis of functional gastrointestinal disorders. Best Pract Res Clin Gastroenterol. 2004;18:633–640
  14. Liebregts T, Adam B, Bertel A, Jones S, Schulze J, Enders C, et al. Effect of E. coli Nissle 1917 on post-inflammatory visceral sensory function in a rat model. Neurogastroenterol Motil. 2005;17:410–414
  15. Dinan TG, Quigley EM, Ahmed SM, Scully P, O’Brien S, O’Mahony L, et al. Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker?. Gastroenterology. 2006;130:304–311
  16. Seatter SC, Li MH, Bubrick MP, West MA. Endotoxin pretreatment of human monocytes alters subsequent endotoxin-triggered release of inflammatory mediators. Shock. 1995;3:252–258
  17. Schattner A, Steinbock M, Tepper R, Schonfeld A, Vaisman N, Hahn T. Tumour necrosis factor production and cell-mediated immunity in anorexia nervosa. Clin Exp Immunol. 1990;79:62–66
  18. Windle HJ, Ang YS, Athie-Morales V, McManus R, Kelleher D. Human peripheral and gastric lymphocyte responses to Helicobacter pylori NapA and AphC differ in infected and uninfected individuals. Gut. 2005;54:25–32
  19. Birkholz S, Knipp U, Nietzki C, Adamek RJ, Opferkuch W. Immunological activity of lipopolysaccharide of Helicobacter pylori on human peripheral mononuclear blood cells in comparison to lipopolysaccharides of other intestinal bacteria. FEMS Immunol Med Microbiol. 1993;6:317–324
  20. Sperber K, Silverstein L, Brusco C, Yoon C, Mullin GE, Mayer L. Cytokine secretion induced by superantigens in peripheral blood mononuclear cells, lamina propria lymphocytes, and intraepithelial lymphocytes. Clin Diagn Lab Immunol. 1995;2:473–477
  21. 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;20:362–370
  22. Nakamura M, Saito H, Kasanuki J, Tamura Y, Yoshida S. Cytokine production in patients with inflammatory bowel disease. Gut. 1992;33:933–937
  23. Holtkamp W, Stollberg T, Reis HE. Serum interleukin-6 is related to disease activity but not disease specificity in inflammatory bowel disease. J Clin Gastroenterol. 1995;20:123–126
  24. Gross V, Andus T, Caesar I, Roth M, Scholmerich J. Evidence for continuous stimulation of interleukin-6 production in Crohn’s disease. Gastroenterology. 1992;102:514–519
  25. Bisping G, Lugering N, Lutke-Brintrup S, Pauels HG, Schurmann G, Domschke W, et al. Patients with inflammatory bowel disease (IBD) reveal increased induction capacity of intracellular interferon-gamma (IFN-gamma) in peripheral CD8+ lymphocytes co-cultured with intestinal epithelial cells. Clin Exp Immunol. 2001;123:15–22
  26. Cario E, Becker A, Sturm A, Goebell H, Dignass AU. Peripheral blood mononuclear cells promote intestinal epithelial restitution in vitro through an interleukin-2/interferon-gamma-dependent pathway. Scand J Gastroenterol. 1999;34:1132–1138
  27. McKay DM, Singh PK. Superantigen activation of immune cells evokes epithelial (T84) transport and barrier abnormalities via IFN-gamma and TNF alpha: inhibition of increased permeability, but not diminished secretory responses by TGF-beta2. J Immunol. 1997;159:2382–2390
  28. Schmitz H, Fromm M, Bode H, Scholz P, Riecken EO, Schulzke JD. Tumor necrosis factor-alpha induces Cl- and K+ secretion in human distal colon driven by prostaglandin E2. Am J Physiol. 1996;271:G669–G674
  29. Oprins JC, van der BC, Meijer HP, Munnik T, Groot JA. Tumour necrosis factor alpha potentiates ion secretion induced by histamine in a human intestinal epithelial cell line and in mouse colon: involvement of the phospholipase D pathway. Gut. 2002;50:314–321
  30. Dunlop SP, Hebden J, Campbell E, Naesdal J, Olbe L, Perkins AC, et al. Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes. Am J Gastroenterol. 2006;101:1288–1294
  31. Gwee KA, Collins SM, Read NW, Rajnakova A, Deng Y, Graham JC, et al. Increased rectal mucosal expression of interleukin 1beta in recently acquired post-infectious irritable bowel syndrome. Gut. 2003;52:523–526
  32. Liebregts T, Adam B, Bertel A, Lackner C, Neumann J, Talley NJ, et al. Psychological stress and the severity of post-inflammatory visceral hyperalgesia. Eur J Pain. 2007;11:216–222
  33. Kaestner F, Hettich M, Peters M, Sibrowski W, Hetzel G, Ponath G, et al. Different activation patterns of proinflammatory cytokines in melancholic and non-melancholic major depression are associated with HPA axis activity. J Affect Disord. 2005;87:305–311
  34. Sykes MA, Blanchard EB, Lackner J, Keefer L, Krasner S. Psychopathology in irritable bowel syndrome: support for a psychophysiological model. J Behav Med. 2003;26:361–372
  35. Maes M, Song C, Lin A, De Jongh R, Van Gastel A, Kenis G, et al. The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety. Cytokine. 1998;10:313–318
  36. Miller GE, Rohleder N, Stetler C, Kirschbaum C. Clinical depression and regulation of the inflammatory response during acute stress. Psychosom Med. 2005;67:679–687
  37. Spath-Schwalbe E, Born J, Schrezenmeier H, Bornstein SR, Stromeyer P, Drechsler S, et al. Interleukin-6 stimulates the hypothalamus-pituitary-adrenocortical axis in man. J Clin Endocrinol Metab. 1994;79:1212–1214
  38. Chrousos GP. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med. 1995;332:1351–1362
  39. Yirmiya R, Pollak Y, Morag M, Reichenberg A, Barak O, Avitsur R, et al. Illness, cytokines, and depression. Ann N Y Acad Sci. 2000;917:478–487
  40. Dunn AJ. Cytokine activation of the HPA axis. Ann N Y Acad Sci. 2000;917:608–617
  41. Moss-Morris R, Spence M. To “lump” or to “split” the functional somatic syndromes: can infectious and emotional risk factors differentiate between the onset of chronic fatigue syndrome and irritable bowel syndrome?. Psychosom Med. 2006;68:463–469
  42. Wichers MC, Kenis G, Leue C, Koek G, Robaeys G, Maes B. Baseline immune activation as a risk factor for the onset of depression during interferon-alpha treatment. Biol Psychiatry. 2007;60:77–79
  43. Kutukculer N, Caglayan S, Aydogdu F. Study of pro-inflammatory (TNF-alpha, IL-1alpha, IL-6) and T-cell-derived (IL-2, IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic arthritis: correlations with clinical and laboratory parameters. Clin Rheumatol. 1998;17:288–292
  44. Schotte H, Schluter B, Willeke P, Mickholz E, Schorat MA, Domschke W, et al. Long-term treatment with etanercept significantly reduces the number of proinflammatory cytokine-secreting peripheral blood mononuclear cells in patients with rheumatoid arthritis. Rheumatology (Oxford). 2004;43:960–964
  45. Chao CC, Janoff EN, Hu SX, Thomas K, Gallagher M, Tsang M, et al. Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome. Cytokine. 1991;3:292–298
  46. Perini F, D’Andrea G, Galloni E, Pignatelli F, Billo G, Alba S, et al. Plasma cytokine levels in migraineurs and controls. Headache. 2005;45:926–931
  47. Svedberg P, Johansson S, Wallander MA, Hamelin B, Pedersen NL. Extra-intestinal manifestations associated with irritable bowel syndrome: a twin study. Aliment Pharmacol Ther. 2002;16:975–983
  48. Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications?. Gastroenterology. 2002;122:1140–1156

 Supported in part by a Royal Adelaide Hospital Clinical Project grant.

PII: S0016-5085(07)00185-0

doi: 10.1053/j.gastro.2007.01.046

Gastroenterology
Volume 132, Issue 3 , Pages 913-920 , March 2007