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Mucosal inflammatory cytokine production by intestinal biopsies in patients with ulcerative colitis and Crohn's disease

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Abstract

Chronic inflammation in inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) may be attributed partly to increased secretion of inflammatory cytokines. The aim of this study was to investigate simultaneously the spontaneous release patterns of tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β), and interleukin-6 (IL-6) by organ cultures of inflamed mucosa from IBD patients. Organ cultures of involved IBD mucosa spontaneously produced increased amounts of TNF-α, IL-1β, and IL-6 compared to normal mucosa. The patterns of cytokine release between Crohn's disease and ulcerative colitis organ cultures were not significantly different. Increased inflammatory cytokine production by lamina propria mononuclear cells (LPMCs) and mucosa treated with EDTA suggests that these cytokines originate mainly from LPMCs. These results confirm the role of inflammatory cytokines in IBD and shed a new light on the role of TNF-α in IBD.

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References

  1. Cominelli F, Nast CC, Duchini A, Lee M: Recombinant interleukin-1 receptor antagonist blocks the proinflammatory activity of endogenous interleukin-1 in rabbit immune colitis. Gastroenterology 103:65–71, 1992

    PubMed  Google Scholar 

  2. Schreiber S, Heinig T, Panzer U, Reinking R, Bouchard A, Stahl PD, Raedler A: Impaired response of activated mononuclear phagocytes to interleukin 4 in inflammatory bowel disease. Gastroenterology 108:21–33, 1995

    PubMed  Google Scholar 

  3. Van Hees PAM, Van Elteren PH, Van Lier HJJ, Van Tongeren JHM: An index of inflammatory activity in patients with Crohn's disease. Gut 21:279–286, 1980

    PubMed  Google Scholar 

  4. Truelove SC, Witts LJ: Cortisone in ulcerative colitis. Final report on a therapeutic trial. Br Med J 2:1041–1048, 1955

    Google Scholar 

  5. Wardle TD, Hall L, Turnberg LA: Use of coculture of colonic mucosal biopsies to investigate the release of eicosanoids by inflamed and uninflamed mucosa from patients with inflammatory bowel disease. Gut 33:1644–1651, 1992

    PubMed  Google Scholar 

  6. Bull DM, Bookman MA: Isolation and functional characterization of human intestinal mucosal lymphoid cells. J Clin Invest 59:966–974, 1977

    PubMed  Google Scholar 

  7. Riley SA, Mani V, Goodman MJ, Dutt S, Herd ME: Microscopic activity in ulcerative colitis: what does it mean? Gut 32:174–178, 1991

    PubMed  Google Scholar 

  8. Kenney JS, Masada MP, Eugui EM, Delustro BM, Mulkins MA, Allison AC: Monoclonal antibodies to human recombinant interleukin 1 (IL1) β: Quantification of IL1β and inhibition of biological activity. J Immunol 138:4236–4242, 1987

    PubMed  Google Scholar 

  9. Stevens C, Walz G, Singaram C, Lipman ML, Zanker B, Muggia A, Antonioli D, Peppercorn MA, Strom TB: Tumor necrosis factor-α, interleukin-1β, interleukin-6 expression in inflammatory bowel disease. Digest Dis Sci 37:818–826, 1992

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  11. MacDonald TT, Hutchings P, Choy M, Murch S, Cooke A: Tumor necrosis factor alpha and interferon gamma production measured at the single cell level in normal and inflammed human intestine. Clin Exp Immunol 80:301–305, 1990

    PubMed  Google Scholar 

  12. Breese EJ, Michie CA, Nicholls SW, Murch SH, Williams CB, Domizio P, Walker-Smith JA, McDonald TT: Tumor necrosis factor-α producing cells in the intestinal mucosa of children with inflammatory bowel disease. Gastroenterology 106:1455–1466, 1994

    PubMed  Google Scholar 

  13. Murch SH, Braegger CP, Walker-Smith JA, MacDonald TT: Location of tumor necrosis factorα by immunohistochemistry in chronic inflammatory bowel disease. Gut 34:1705–1709, 1993

    PubMed  Google Scholar 

  14. Jones SC, Haidar A, Hagan P, Crabtree JE, Banks RE, Axon ATR, Dixon MF, Whicher JT: Cytokine production in the mucosa of patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 5:607–612, 1993

    Google Scholar 

  15. Autschbach F, Schürmann G, Qiao L, Merz H, Wallich R, Meuer SC: Cytokine messenger RNA expression and proliferation status of intestinal mononuclear cells in noninflamed gut and Crohn's disease. Virchows Arch 426:51–61, 1995

    PubMed  Google Scholar 

  16. Powrie F, Correa-Oliveira R, Mauze S, Coffman RL: Regulatory interactions between CD45RBhi and CD45RBlo CD4+ T cells are important for the balance between protective and pathogenic cell-mediated immunity. J Exp Med 179:589–600, 1994

    PubMed  Google Scholar 

  17. Powrie F, Leach MW, Mauze S, Menon S, Caddle LB, Coffman RL: Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. Immunity 1:553–562, 1994

    PubMed  Google Scholar 

  18. Van Dullemen HM, Van Deventer SJH, Hommes DW, Bijl HA, Jansen J, Tytgat GNJ, Woody J: Treatment of Crohn's disease with anti-tumor necrosis factor chymeric monoclonal antibody (cA2). Gastroenterology 109:129–135, 1995

    PubMed  Google Scholar 

  19. Yougman KR, Simon PhL, West GA, Cominelli F, Rachmilewitz D, Klein JS, Fiocchi C: Localization of intestinal interleukin 1 activity and protein and gene expression to lamina propria cells. Gastroenterology 104:749–758, 1993

    PubMed  Google Scholar 

  20. Reinecker HC, Steffen M, Witthoeft T, Pflueger I, Schreiber S, McDermott RP, Raedler A: Enhanced secretion of tumor necrosis factor-alpha, IL-6, and IL-1β by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease. Clin Exp Immunol 94:174–181, 1993

    PubMed  Google Scholar 

  21. Mahida YR, Wu K, Jewell DP: Enhanced production of interleukin 1 beta by mononuclear cells isolated from mucosa with active ulcerative colitis or Crohn's disease. Gut 30:835–838, 1989

    PubMed  Google Scholar 

  22. Ligumsky M, Simon PL, Karmeli F, Rachmilewitz D: Role of interleukin 1 in inflammatory bowel disease-enhanced production during active disease. Gut 31:686–689, 1990

    PubMed  Google Scholar 

  23. Brynskov J, Tvede N, Anderson CB, Vilien M: Increased concentration of interleukin-1-β, interleukin-2, and soluble interleukin-2 receptor in endoscopical mucosal biopsy specimens with active inflammatory bowel disease. Gut 33:55–58, 1992

    PubMed  Google Scholar 

  24. McCabe RP, Secrist H, Botney M, Egan M, Peters MG: Cytokine mRNA expression in intestine from normal and inflammatory bowel disease patients. Clin Immunol Immunopathol 66:52–58, 1993

    PubMed  Google Scholar 

  25. Nishiyama T, Mitsuyama K, Toyonaga A, Sasaki E, Tanikawa K: Colonic mucosal interleukin 1 receptor antagonist in inflammatory bowel disease. Digestion 55:368–373, 1994

    PubMed  Google Scholar 

  26. Casini-Raggi V, Kam L, Chong YJT, Fiocchi C, Pizarro TT, Cominelli F: Mucosal imbalance of IL1 and IL1 receptor antagonist in inflammatory bowel disease. J Immunol 154:2434–2440, 1995

    PubMed  Google Scholar 

  27. Mitsuyama K, Sasaki E, Toyonaga A, Ikeda H, Tsuruta O, Irie A, Arima N, Oriishi T, Harada K, Fujisaki K, Sata M, Tanikawa K: Colonic mucosal interleukin-6 in inflammatory bowel disease. Digestion 50:104–111, 1991

    PubMed  Google Scholar 

  28. Kusugami K, Fukatsu A, Tanimoto M, Shinoda M, Haruta JI, Kuroiwa A, Ina K, Kanayama K, Ando T, Matsuura T, Yamaguchi T, Morise K, Ieda M, Iokawa H, Ishihara A, Sarai A: Elevation of interleukin-6 in inflammatory bowel disease is macrophage- and epithelial cell-dependent. Digest Dis Sci 40:949–959, 1995

    PubMed  Google Scholar 

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Reimund, J.M., Wittersheim, C., Dumont, S. et al. Mucosal inflammatory cytokine production by intestinal biopsies in patients with ulcerative colitis and Crohn's disease. J Clin Immunol 16, 144–150 (1996). https://doi.org/10.1007/BF01540912

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  • DOI: https://doi.org/10.1007/BF01540912

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