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Increased cytokine transcripts in pouchitis reflect the degree of inflammation but not the underlying entity

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Abstract

Background and aims

After ileopouch anal anastomosis (IPAA), 10–40% of patients with ulcerative colitis (UC) but only 5% of patients with familial adenomatous polyposis (FAP) develop pouchitis. Immunoregulatory abnormalities might be of importance in the pathogenesis of the disease. Therefore, we characterized cytokine and chemokine transcripts in inflamed and non-inflamed pouches in patients with UC compared to those with FAP and Crohn's disease (CD).

Patients and methods

Mucosal biopsies were taken from 87 patients with IPAA [UC (n=70), CD (n=8) or FAP (n=9)]. Patients with active ileal CD (n=14), active UC (n=17) and non-inflammatory conditions (n=12) served as controls. The expression of 20 gene transcripts was quantified using real-time polymerase chain reaction.

Results and findings

Pro-inflammatory cytokines and chemokines are significantly increased in IPAA patients with acute pouchitis. This increase is independent of the underlying disease (UC or CD) and reflects the degree of inflammation. A good correlation between pouchitis activity (using the Pouchitis Disease Activity Index) and the MRP-14, interleukin-8, macrophage inflammatory protein-2α and matrix metalloproteinase-1 transcripts was observed.

Interpretations and conclusions

Our data support the view that pouchitis reflects an inflammatory process that is different from that of underlying inflammatory bowel diseases, as the cytokine and chemokine patterns in pouchitis are neither typical of CD nor of UC, but maybe due to bacterial intestinal microflora overgrowth in the pouch lumen. Quantification of transcript levels allows an estimation of the extent of mucosal inflammation and may become helpful in the evaluation of the disease, especially in clinical trials.

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References

  1. Mahadevan U, Sandborn WJ (2003) Diagnosis and management of pouchitis. Gastroenterology 124:1636–1650

    Article  PubMed  Google Scholar 

  2. Kühbacher T, Schreiber S, Runkel N (1998) Pouchitis: pathophysiology and treatment. Int J Colorectal Dis 13:96–207

    Google Scholar 

  3. Von Herbay A, Stern J, Buhr H et al (1994) Heterogeneity of pouchitis after restorative proctocolectomy for ulcerative colitis. Gastroenterology 106:A790 (Abstract)

    Google Scholar 

  4. Perrault J, Berry G, Greseth J et al (1997) Pouchitis in young patients after the ileal pouch anal anastomosis. Inflamm Bowel Dis 3:181–185

    Article  Google Scholar 

  5. Hurst RD, Molinari M, Chung TP et al (1996) Prospective study of the incidence, timing and treatment of pouchitis in 104 consecutive patients after restorative proctocolectomy. Arch Surg 131:487–500

    Google Scholar 

  6. Patel RT, Bain I, Youngs D et al (1995) Cytokine production in pouchitis is similar to that in ulcerative colitis. Dis Colon Rectum 38:831–837

    Article  PubMed  CAS  Google Scholar 

  7. Gionchetti P, Campieri M, Belluzzi A et al (1994) Mucosal concentrations of interleukin-1beta, interleukin-6, interleukin-8, and tumor necrosis factor-alpha in pelvic ileal pouches. Dig Dis Sci 39:1525–1531

    Article  Google Scholar 

  8. De Silva HJ, Jones M, Prince C (1991) Lymphocyte and macrophage subpopulations in pelvic ileal pouches. Gut 32:1160–1165

    Article  PubMed  Google Scholar 

  9. Mahida YR, Patel S, Gionchetti P et al (1989) Macrophage subpopulations in lamina propria of normal and inflamed colon and terminal ileum. Gut 30:826–834

    Article  PubMed  CAS  Google Scholar 

  10. Campbell AP, Merrett MN, Kettlewell M et al (1994) Expression of colonic antigens by goblet and columnar epithelial cells in ileal pouch mucosa: their association with inflammatory change and faecal stasis. J Clin Pathol 47:834–838

    Article  PubMed  CAS  Google Scholar 

  11. Stallmach A, Schäfer F, Hoffmann S et al (1989) Increased state of activation of CD 4 positive T cells and elevated interferon γ production in pouchitis. Gut 43:499–505

    Article  Google Scholar 

  12. Schreiber S, Raedler A, Conn AF et al (1992) Increased release of soluble interleukin-2 receptor by colonic lamina propria mononuclear cells in inflammatory bowel disease. Gut 32:236–241

    Article  Google Scholar 

  13. Evgenikos N, Bartolo DC, Hamer-Hodges DW et al (2002) Assessment of ileoanal pouch inflammation by interleukin 1beta and interleukin 8 concentrations in the gut lumen. Dis Colon Rectum 45:249–255

    Article  PubMed  CAS  Google Scholar 

  14. Evgenikos NL, Bartolo DC, Hamer-Hodges DW et al (2000) Luminal neutrophil migration in ileoanal pouches studied by whole gut lavage. Eur J Gastroenterol Hepatol 12:553–557

    PubMed  CAS  Google Scholar 

  15. Stallmach A, Chan CC, Ecker FW et al (2000) Comparable expression of matrix metalloproteinases 1 and 2 in pouchitis and ulcerative colitis. Gut 47:415–422

    Article  PubMed  CAS  Google Scholar 

  16. Stallmach A, van Look M, Scheiffele F et al (1999) IgG, albumin, and sCD44 in whole-gut fluid are useful clinical markers for assessing the presence and activity of pouchitis. Int J Colorectal Dis 14:35–40

    Article  PubMed  CAS  Google Scholar 

  17. Brynskov J, Tvede N, Andersen CB et al (1992) Increased concentrations of interleukin 1β, interleukin 2, and soluble interleukin-2 receptors in endoscopic mucosal biopsy specimens with active inflammatory bowel disease. Gut 33:55–58

    Article  PubMed  CAS  Google Scholar 

  18. Pullman WE, Elsbury S, Masanobu K et al (1992) Enhanced mucosal cytokine production in inflammatory bowel disease. Gastroenterology 102:529–537

    PubMed  CAS  Google Scholar 

  19. Reinecker HC, Steffen M, Witthoeft T et al (1993) Enhanced secretion of tumor necrosis factor alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease. Clin Exp Immunol 94:174–181

    PubMed  CAS  Google Scholar 

  20. Stevens C, Walz G, Singaram C et al (1992) Tumor necrosis factor-α, interleukin-1β and interleukin 6 expression in inflammatory bowel disease. Dig Dis Sci 37:818–826

    Article  PubMed  CAS  Google Scholar 

  21. Isaacs KL, Sartor RB, Haskill S (1992) Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification. Gastroenterology 103:1587–1595

    PubMed  CAS  Google Scholar 

  22. Woywodt A, Neustock P, Kruse A et al (1994) Cytokine expression in intestinal mucosal biopsies. In situ hybridisation of the mRNA for interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in inflammatory bowel disease. Eur Cytokine Netw 5:387–395

    PubMed  CAS  Google Scholar 

  23. Stallmach A, Giese T, Schmidt C et al (2004) Cytokine/chemokine transcript profiles reflect mucosal inflammation in Crohn's disease. Int J Colorectal Dis 19:308–315

    Article  PubMed  Google Scholar 

  24. Sandborn WJ, Tremaine WJ, Batts KP et al (1994) Pouchitis after ileal pouch-anal anastomosis: a Pouchitis Disease Activity Index. Mayo Clin Proc 69:409–515

    PubMed  CAS  Google Scholar 

  25. Kock NG, Darle N, Hulten L et al (1977) Ileostomy. Curr Probl Surg 14:1–52

    Article  PubMed  CAS  Google Scholar 

  26. Fiocchi C (1998) Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 115(1):182–205

    Article  PubMed  CAS  Google Scholar 

  27. Sartor RB (1991) Pathogenetic and clinical relevance of cytokines in inflammatory bowel disease. Immunol Res 10(3–4):465–471

    PubMed  CAS  Google Scholar 

  28. Gately MK, Renzetti LM, Magram J et al (1998) The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. Annu Rev Immunol 16:495–521

    Article  PubMed  CAS  Google Scholar 

  29. Kobayashi M, Fitz L, Ryan M et al (1989) Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biological effects on human lymphocytes. J Exp Med 170:827–845

    Article  PubMed  CAS  Google Scholar 

  30. Wolf SF, Temple PA, Kobayashi M et al (1991) Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J Immunol 146:3074–3081

    PubMed  CAS  Google Scholar 

  31. Desreumaux P, Brandt E, Gambiez L et al (1997) Distinct cytokine patterns in early ileal lesions of Crohn's disease. Gastroenterology 113:118–126

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by grants from the Bundesministerium für Bildung und Forschung (“Network of competence: chronic inflammatory bowel disease”; “molecular markers” and “pouchitis” working groups). The authors thank the nursing staff of the Endoscopy Department.

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Correspondence to A. Stallmach.

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Schmidt, C., Giese, T., Ludwig, B. et al. Increased cytokine transcripts in pouchitis reflect the degree of inflammation but not the underlying entity. Int J Colorectal Dis 21, 419–426 (2006). https://doi.org/10.1007/s00384-005-0024-2

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