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Gut. Nov 1996; 39(5): 684–689.
PMCID: PMC1383392

Increased production of tumour necrosis factor-alpha interleukin-1 beta, and interleukin-6 by morphologically normal intestinal biopsies from patients with Crohn's disease.

Abstract

BACKGROUND: Increasing evidence points to a important role for inflammatory cytokines for the pathogenesis of Crohn's disease. AIM: To compare the secretion rate of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by morphologically normal and inflamed intestinal mucosa from patients with Crohn's disease. RESULTS: Organ cultures of intestinal biopsy specimens taken from areas of affected mucosa from patients with Crohn's disease spontaneously produced increased amounts of TNF-alpha, IL-1 beta, and IL-6 compared with controls but also biopsy specimens taken in macroscopically and microscopically unaffected areas in the same patients. Concentrations of IL-1 beta and IL-6 measured in the supernatant fluid of biopsy cultures were positively correlated with the degree of tissue involvement measured by both endoscopic and histological grading. By contrast, TNF-alpha concentrations were not correlated to endoscopic and histological grading. CONCLUSIONS: These consistently raised TNF-alpha, IL-1 beta and IL-6 secretions by normal appearing mucosa from patients with Crohn's disease provide evidence for a sustained immune stimulation in Crohn's disease even in the absence of patent inflammation. The results shed a new light on the role of inflammatory cytokines in the onset of intestinal tissue damage in Crohn's disease and suggest that the range of intestinal lesions in Crohn's disease may be wider than suspected on the basis of regular endoscopic and histological examinations.

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  • Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M. Predictability of the postoperative course of Crohn's disease. Gastroenterology. 1990 Oct;99(4):956–963. [PubMed]
  • Dyer NH, Stansfeld AG, Dawson AM. The value of rectal biopsy in the diagnosis of Crohn's disease. Scand J Gastroenterol. 1970;5(6):491–496. [PubMed]
  • Reinecker HC, Steffen M, Witthoeft T, Pflueger I, Schreiber S, MacDermott RP, Raedler A. Enhanced secretion of tumour 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. 1993 Oct;94(1):174–181. [PMC free article] [PubMed]
  • Kusugami K, Fukatsu A, Tanimoto M, Shinoda M, Haruta J, Kuroiwa A, Ina K, Kanayama K, Ando T, Matsuura T, et al. Elevation of interleukin-6 in inflammatory bowel disease is macrophage- and epithelial cell-dependent. Dig Dis Sci. 1995 May;40(5):949–959. [PubMed]
  • Reimund JM, Wittersheim C, Dumont S, Muller CD, Baumann R, Poindron P, Duclos B. Mucosal inflammatory cytokine production by intestinal biopsies in patients with ulcerative colitis and Crohn's disease. J Clin Immunol. 1996 May;16(3):144–150. [PubMed]
  • van Hees PA, van Elteren PH, van Lier HJ, van Tongeren JH. An index of inflammatory activity in patients with Crohn's disease. Gut. 1980 Apr;21(4):279–286. [PMC free article] [PubMed]
  • 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. 1992 Dec;33(12):1644–1651. [PMC free article] [PubMed]
  • Dunnill MS, Whitehead R. A method for the quantitation of small intestinal biopsy specimens. J Clin Pathol. 1972 Mar;25(3):243–246. [PMC free article] [PubMed]
  • Dunne WT, Cooke WT, Allan RN. Enzymatic and morphometric evidence for Crohn's disease as a diffuse lesion of the gastrointestinal tract. Gut. 1977 Apr;18(4):290–294. [PMC free article] [PubMed]
  • Riley SA, Mani V, Goodman MJ, Dutt S, Herd ME. Microscopic activity in ulcerative colitis: what does it mean? Gut. 1991 Feb;32(2):174–178. [PMC free article] [PubMed]
  • Kenney JS, Masada MP, Eugui EM, Delustro BM, Mulkins MA, Allison AC. Monoclonal antibodies to human recombinant interleukin 1 (IL 1)beta: quantitation of IL 1 beta and inhibition of biological activity. J Immunol. 1987 Jun 15;138(12):4236–4242. [PubMed]
  • Mahida YR, Wu K, Jewell DP. Enhanced production of interleukin 1-beta by mononuclear cells isolated from mucosa with active ulcerative colitis of Crohn's disease. Gut. 1989 Jun;30(6):835–838. [PMC free article] [PubMed]
  • Ligumsky M, Simon PL, Karmeli F, Rachmilewitz D. Role of interleukin 1 in inflammatory bowel disease--enhanced production during active disease. Gut. 1990 Jun;31(6):686–689. [PMC free article] [PubMed]
  • Stevens C, Walz G, Singaram C, Lipman ML, Zanker B, Muggia A, Antonioli D, Peppercorn MA, Strom TB. Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 expression in inflammatory bowel disease. Dig Dis Sci. 1992 Jun;37(6):818–826. [PubMed]
  • Isaacs KL, Sartor RB, Haskill S. Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification. Gastroenterology. 1992 Nov;103(5):1587–1595. [PubMed]
  • Breese EJ, Michie CA, Nicholls SW, Murch SH, Williams CB, Domizio P, Walker-Smith JA, MacDonald TT. Tumor necrosis factor alpha-producing cells in the intestinal mucosa of children with inflammatory bowel disease. Gastroenterology. 1994 Jun;106(6):1455–1466. [PubMed]
  • 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. 1995;426(1):51–60. [PubMed]
  • van Dullemen HM, van Deventer SJ, Hommes DW, Bijl HA, Jansen J, Tytgat GN, Woody J. Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology. 1995 Jul;109(1):129–135. [PubMed]
  • Sher ME, D'Angelo AJ, Stein TA, Bailey B, Burns G, Wise L. Cytokines in Crohn's colitis. Am J Surg. 1995 Jan;169(1):133–136. [PubMed]
  • 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. 1995 Jan;108(1):21–33. [PubMed]
  • Goodman MJ, Skinner JM, Truelove SC. Abnormalities in the apparently normal bowel mucosa in Crohn's disease. Lancet. 1976 Feb 7;1(7954):275–278. [PubMed]
  • Ahrenstedt O, Knutson L, Nilsson B, Nilsson-Ekdahl K, Odlind B, Hällgren R. Enhanced local production of complement components in the small intestines of patients with Crohn's disease. N Engl J Med. 1990 May 10;322(19):1345–1349. [PubMed]
  • Olaison G, Sjödahl R, Tagesson C. Increased phospholipase A2 activity of Ileal mucosa in Crohn's disease. Digestion. 1988;41(3):136–141. [PubMed]
  • Nagel E, Bartels M, Pichlmayr R. Scanning electron-microscopic lesions in Crohn's disease: relevance for the interpretation of postoperative recurrence. Gastroenterology. 1995 Feb;108(2):376–382. [PubMed]
  • Dvorak AM, Connell AB, Dickersin GR. Crohn's disease: a scanning electron microscopic study. Hum Pathol. 1979 Mar;10(2):165–177. [PubMed]
  • Majno G, Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol. 1995 Jan;146(1):3–15. [PMC free article] [PubMed]
  • Breese E, Braegger CP, Corrigan CJ, Walker-Smith JA, MacDonald TT. Interleukin-2- and interferon-gamma-secreting T cells in normal and diseased human intestinal mucosa. Immunology. 1993 Jan;78(1):127–131. [PMC free article] [PubMed]
  • Kindler V, Sappino AP, Grau GE, Piguet PF, Vassalli P. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell. 1989 Mar 10;56(5):731–740. [PubMed]

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