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Gut. 1993 December; 34(12): 1705–1709.
PMCID: PMC1374467

Location of tumour necrosis factor alpha by immunohistochemistry in chronic inflammatory bowel disease.

Abstract

This study determined the location and tissue density of cells immunoreactive for tumour necrosis factor alpha (TNF alpha) in intestinal specimens from 24 patients with chronic inflammatory bowel disease (15 with Crohn's disease, nine with ulcerative colitis) and 11 controls. There was significantly increased density of TNF alpha immunoreactive cells in the lamina propria of both ulcerative colitis and Crohn's disease specimens, although the distribution of these cells differed in the two conditions. In ulcerative colitis most of the TNF alpha immunoreactivity was seen in the subepithelial macrophages, with comparatively less in the deep lamina propria, while in Crohn's disease immunoreactive cells were distributed evenly throughout the lamina propria. Increased submucosal immunoreactivity was found only in Crohn's disease, in which TNF alpha positive macrophages tended to cluster around arterioles and venules, often infiltrating and disrupting vascular endothelium. It is suggested that this degree of TNF alpha production probably contributes significantly to the pathogenesis of both Crohn's disease and ulcerative colitis, by impairing the integrity of epithelial and endothelial membranes, increasing inflammatory cell recruitment, and by prothrombotic effects on the vascular endothelium.

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Selected References

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  • Selby WS, Poulter LW, Hobbs S, Jewell DP, Janossy G. Heterogeneity of HLA-DR-positive histiocytes in human intestinal lamina propria: a combined histochemical and immunohistological analysis. J Clin Pathol. 1983 Apr;36(4):379–384. [PMC free article] [PubMed]
  • Allison MC, Cornwall S, Poulter LW, Dhillon AP, Pounder RE. Macrophage heterogeneity in normal colonic mucosa and in inflammatory bowel disease. Gut. 1988 Nov;29(11):1531–1538. [PMC free article] [PubMed]
  • Mahida YR, Patel S, Wu K, Jewell DP. Interleukin 2 receptor expression by macrophages in inflammatory bowel disease. Clin Exp Immunol. 1988 Dec;74(3):382–386. [PubMed]
  • Mahida YR, Wu KC, Jewell DP. Respiratory burst activity of intestinal macrophages in normal and inflammatory bowel disease. Gut. 1989 Oct;30(10):1362–1370. [PMC free article] [PubMed]
  • Choy MY, Walker-Smith JA, Williams CB, MacDonald TT. Differential expression of CD25 (interleukin-2 receptor) on lamina propria T cells and macrophages in the intestinal lesions in Crohn's disease and ulcerative colitis. Gut. 1990 Dec;31(12):1365–1370. [PMC free article] [PubMed]
  • Halstensen TS, Mollnes TE, Garred P, Fausa O, Brandtzaeg P. Epithelial deposition of immunoglobulin G1 and activated complement (C3b and terminal complement complex) in ulcerative colitis. Gastroenterology. 1990 May;98(5 Pt 1):1264–1271. [PubMed]
  • Malizia G, Calabrese A, Cottone M, Raimondo M, Trejdosiewicz LK, Smart CJ, Oliva L, Pagliaro L. Expression of leukocyte adhesion molecules by mucosal mononuclear phagocytes in inflammatory bowel disease. Gastroenterology. 1991 Jan;100(1):150–159. [PubMed]
  • Pullman WE, Elsbury S, Kobayashi M, Hapel AJ, Doe WF. Enhanced mucosal cytokine production in inflammatory bowel disease. Gastroenterology. 1992 Feb;102(2):529–537. [PubMed]
  • MacDonald TT, Hutchings P, Choy MY, Murch S, Cooke A. Tumour necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine. Clin Exp Immunol. 1990 Aug;81(2):301–305. [PubMed]
  • Cappello M, Keshav S, Prince C, Jewell DP, Gordon S. Detection of mRNAs for macrophage products in inflammatory bowel disease by in situ hybridisation. Gut. 1992 Sep;33(9):1214–1219. [PMC free article] [PubMed]
  • Murch SH, Lamkin VA, Savage MO, Walker-Smith JA, MacDonald TT. Serum concentrations of tumour necrosis factor alpha in childhood chronic inflammatory bowel disease. Gut. 1991 Aug;32(8):913–917. [PMC free article] [PubMed]
  • 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. 1992 Jul;103(1):65–71. [PubMed]
  • Braegger CP, Nicholls S, Murch SH, Stephens S, MacDonald TT. Tumour necrosis factor alpha in stool as a marker of intestinal inflammation. Lancet. 1992 Jan 11;339(8785):89–91. [PubMed]
  • Exley AR, Cohen J, Buurman W, Owen R, Hanson G, Lumley J, Aulakh JM, Bodmer M, Riddell A, Stephens S, et al. Monoclonal antibody to TNF in severe septic shock. Lancet. 1990 May 26;335(8700):1275–1277. [PubMed]
  • Engelberts I, Möller A, Schoen GJ, van der Linden CJ, Buurman WA. Evaluation of measurement of human TNF in plasma by ELISA. Lymphokine Cytokine Res. 1991 Apr;10(1-2):69–76. [PubMed]
  • Lennox B. Observations on the accuracy of point counting including a description of a new graticule. J Clin Pathol. 1975 Feb;28(2):99–103. [PMC free article] [PubMed]
  • Mullin JM, Snock KV. Effect of tumor necrosis factor on epithelial tight junctions and transepithelial permeability. Cancer Res. 1990 Apr 1;50(7):2172–2176. [PubMed]
  • Deem RL, Shanahan F, Targan SR. Triggered human mucosal T cells release tumour necrosis factor-alpha and interferon-gamma which kill human colonic epithelial cells. Clin Exp Immunol. 1991 Jan;83(1):79–84. [PubMed]
  • Schiller JH, Bittner G, Storer B, Willson JK. Synergistic antitumor effects of tumor necrosis factor and gamma-interferon on human colon carcinoma cell lines. Cancer Res. 1987 Jun 1;47(11):2809–2813. [PubMed]
  • Doukas J, Pober JS. IFN-gamma enhances endothelial activation induced by tumor necrosis factor but not IL-1. J Immunol. 1990 Sep 15;145(6):1727–1733. [PubMed]
  • Kvale D, Brandtzaeg P, Løvhaug D. Up-regulation of the expression of secretory component and HLA molecules in a human colonic cell line by tumour necrosis factor-alpha and gamma interferon. Scand J Immunol. 1988 Sep;28(3):351–357. [PubMed]
  • Ding AH, Nathan CF, Stuehr DJ. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol. 1988 Oct 1;141(7):2407–2412. [PubMed]
  • Hollander D. Crohn's disease--a permeability disorder of the tight junction? Gut. 1988 Dec;29(12):1621–1624. [PMC free article] [PubMed]
  • Rutgeerts P, Goboes K, Peeters M, Hiele M, Penninckx F, Aerts R, Kerremans R, Vantrappen G. Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum. Lancet. 1991 Sep 28;338(8770):771–774. [PubMed]
  • Halstensen TS, Das KM, Brandtzaeg P. Epithelial deposits of immunoglobulin G1 and activated complement colocalise with the M(r) 40 kD putative autoantigen in ulcerative colitis. Gut. 1993 May;34(5):650–657. [PMC free article] [PubMed]
  • Matthes H, Herbst H, Schuppan D, Stallmach A, Milani S, Stein H, Riecken EO. Cellular localization of procollagen gene transcripts in inflammatory bowel diseases. Gastroenterology. 1992 Feb;102(2):431–442. [PubMed]
  • Halstensen TS, Mollnes TE, Brandtzaeg P. Persistent complement activation in submucosal blood vessels of active inflammatory bowel disease: immunohistochemical evidence. Gastroenterology. 1989 Jul;97(1):10–19. [PubMed]
  • Nawroth PP, Bank I, Handley D, Cassimeris J, Chess L, Stern D. Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1363–1375. [PMC free article] [PubMed]
  • Strieter RM, Kunkel SL, Showell HJ, Remick DG, Phan SH, Ward PA, Marks RM. Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-alpha, LPS, and IL-1 beta. Science. 1989 Mar 17;243(4897):1467–1469. [PubMed]
  • Brett J, Gerlach H, Nawroth P, Steinberg S, Godman G, Stern D. Tumor necrosis factor/cachectin increases permeability of endothelial cell monolayers by a mechanism involving regulatory G proteins. J Exp Med. 1989 Jun 1;169(6):1977–1991. [PMC free article] [PubMed]
  • Moore KL, Esmon CT, Esmon NL. Tumor necrosis factor leads to the internalization and degradation of thrombomodulin from the surface of bovine aortic endothelial cells in culture. Blood. 1989 Jan;73(1):159–165. [PubMed]
  • Nawroth PP, Stern DM. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med. 1986 Mar 1;163(3):740–745. [PMC free article] [PubMed]
  • Schleef RR, Bevilacqua MP, Sawdey M, Gimbrone MA, Jr, Loskutoff DJ. Cytokine activation of vascular endothelium. Effects on tissue-type plasminogen activator and type 1 plasminogen activator inhibitor. J Biol Chem. 1988 Apr 25;263(12):5797–5803. [PubMed]
  • Bevilacqua MP, Pober JS, Majeau GR, Fiers W, Cotran RS, Gimbrone MA., Jr Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4533–4537. [PubMed]
  • Bach R, Nemerson Y, Konigsberg W. Purification and characterization of bovine tissue factor. J Biol Chem. 1981 Aug 25;256(16):8324–8331. [PubMed]
  • van der Poll T, Büller HR, ten Cate H, Wortel CH, Bauer KA, van Deventer SJ, Hack CE, Sauerwein HP, Rosenberg RD, ten Cate JW. Activation of coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med. 1990 Jun 7;322(23):1622–1627. [PubMed]
  • Gerlach H, Lieberman H, Bach R, Godman G, Brett J, Stern D. Enhanced responsiveness of endothelium in the growing/motile state to tumor necrosis factor/cachectin. J Exp Med. 1989 Sep 1;170(3):913–931. [PMC free article] [PubMed]
  • Wakefield AJ, Sawyerr AM, Dhillon AP, Pittilo RM, Rowles PM, Lewis AA, Pounder RE. Pathogenesis of Crohn's disease: multifocal gastrointestinal infarction. Lancet. 1989 Nov 4;2(8671):1057–1062. [PubMed]
  • Murch SH, Braegger CP, Sessa WC, MacDonald TT. High endothelin-1 immunoreactivity in Crohn's disease and ulcerative colitis. Lancet. 1992 Feb 15;339(8790):381–385. [PubMed]
  • Ding A, Nathan CF, Graycar J, Derynck R, Stuehr DJ, Srimal S. Macrophage deactivating factor and transforming growth factors-beta 1 -beta 2 and -beta 3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-gamma. J Immunol. 1990 Aug 1;145(3):940–944. [PubMed]
  • Bogdan C, Vodovotz Y, Nathan C. Macrophage deactivation by interleukin 10. J Exp Med. 1991 Dec 1;174(6):1549–1555. [PMC free article] [PubMed]
  • Sampaio EP, Sarno EN, Galilly R, Cohn ZA, Kaplan G. Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J Exp Med. 1991 Mar 1;173(3):699–703. [PMC free article] [PubMed]
  • Vogelsang GB, Farmer ER, Hess AD, Altamonte V, Beschorner WE, Jabs DA, Corio RL, Levin LS, Colvin OM, Wingard JR, et al. Thalidomide for the treatment of chronic graft-versus-host disease. N Engl J Med. 1992 Apr 16;326(16):1055–1058. [PubMed]
  • Larsson H. Treatment of severe colitis in Behçet's syndrome with thalidomide (CG-217). J Intern Med. 1990 Oct;228(4):405–407. [PubMed]

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