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Gut. 1997 April; 40(4): 470–474.
PMCID: PMC1027120

Treatment with tumour necrosis factor inhibitor oxpentifylline does not improve corticosteroid dependent chronic active Crohn's disease.

Abstract

BACKGROUND: In Crohn's disease, inflammation is presumably sustained by an increased production of proinflammatory cytokines, in particular tumour necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL 1 beta). TNF alpha can induce a host of cellular effector events resulting in perpetuation of the inflammatory process. In vivo studies with anti-TNF alpha antibody treatment have led to impressive clinical results. AIMS: To investigate whether treatment with the TNF alpha inhibitor oxpentifylline results in clinical improvement in corticosteroid dependent chronic active Crohn's disease. METHODS: Sixteen Crohn's disease patients received oxpentifylline 400 mg four times a day in a four week open label study. RESULTS: Blockade of TNF alpha production in 16 patients with corticosteroid dependent Crohn's disease did not improve the clinical disease activity (CDAI mean (SEM) 188.75 (5.65) versus 185.13 (10.87) or the endoscopic degree of inflammation (CDEIS 14.9 (2.87) versus 14.8 (2.27) or laboratory parameters. CONCLUSIONS: In this study, use of the TNF alpha inhibitor oxpentifylline does not improve inflammation in Crohn's disease. This finding suggests that there may be more key mediators than only TNF alpha in the inflammatory process in Crohn's disease.

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Selected References

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  • 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]
  • 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]
  • Schreiber S, MacDermott RP, Raedler A, Pinnau R, Bertovich MJ, Nash GS. Increased activation of isolated intestinal lamina propria mononuclear cells in inflammatory bowel disease. Gastroenterology. 1991 Oct;101(4):1020–1030. [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]
  • 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]
  • Dinarello CA, Wolff SM. The role of interleukin-1 in disease. N Engl J Med. 1993 Jan 14;328(2):106–113. [PubMed]
  • Rampart M, De Smet W, Fiers W, Herman AG. Inflammatory properties of recombinant tumor necrosis factor in rabbit skin in vivo. J Exp Med. 1989 Jun 1;169(6):2227–2232. [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]
  • Amiri P, Locksley RM, Parslow TG, Sadick M, Rector E, Ritter D, McKerrow JH. Tumour necrosis factor alpha restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice. Nature. 1992 Apr 16;356(6370):604–607. [PubMed]
  • Sun XM, Hsueh W. Bowel necrosis induced by tumor necrosis factor in rats is mediated by platelet-activating factor. J Clin Invest. 1988 May;81(5):1328–1331. [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]
  • 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]
  • 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]
  • 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]
  • 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]
  • 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]
  • Hyams JS, Treem WR, Eddy E, Wyzga N, Moore RE. Tumor necrosis factor-alpha is not elevated in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 1991 Feb;12(2):233–236. [PubMed]
  • Derkx B, Taminiau J, Radema S, Stronkhorst A, Wortel C, Tytgat G, van Deventer S. Tumour-necrosis-factor antibody treatment in Crohn's disease. Lancet. 1993 Jul 17;342(8864):173–174. [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]
  • Strieter RM, Remick DG, Ward PA, Spengler RN, Lynch JP, 3rd, Larrick J, Kunkel SL. Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxifylline. Biochem Biophys Res Commun. 1988 Sep 30;155(3):1230–1236. [PubMed]
  • Bianco JA, Appelbaum FR, Nemunaitis J, Almgren J, Andrews F, Kettner P, Shields A, Singer JW. Phase I-II trial of pentoxifylline for the prevention of transplant-related toxicities following bone marrow transplantation. Blood. 1991 Sep 1;78(5):1205–1211. [PubMed]
  • Dezube BJ, Pardee AB, Chapman B, Beckett LA, Korvick JA, Novick WJ, Chiurco J, Kasdan P, Ahlers CM, Ecto LT, et al. Pentoxifylline decreases tumor necrosis factor expression and serum triglycerides in people with AIDS. NIAID AIDS Clinical Trials Group. J Acquir Immune Defic Syndr. 1993 Jul;6(7):787–794. [PubMed]
  • Tilg H, Eibl B, Pichl M, Gächter A, Herold M, Brankova J, Huber C, Niederwieser D. Immune response modulation by pentoxifylline in vitro. Transplantation. 1993 Jul;56(1):196–201. [PubMed]
  • van Leenen D, van der Poll T, Levi M, ten Cate H, van Deventer SJ, Hack CE, Aarden LA, ten Cate JW. Pentoxifylline attenuates neutrophil activation in experimental endotoxemia in chimpanzees. J Immunol. 1993 Aug 15;151(4):2318–2325. [PubMed]
  • Breuillé D, Farge MC, Rosé F, Arnal M, Attaix D, Obled C. Pentoxifylline decreases body weight loss and muscle protein wasting characteristics of sepsis. Am J Physiol. 1993 Oct;265(4 Pt 1):E660–E666. [PubMed]
  • Attal M, Huguet F, Rubie H, Charlet JP, Schlaifer D, Huynh A, Laurent G, Pris J. Prevention of regimen-related toxicities after bone marrow transplantation by pentoxifylline: a prospective, randomized trial. Blood. 1993 Aug 1;82(3):732–736. [PubMed]
  • Han J, Thompson P, Beutler B. Dexamethasone and pentoxifylline inhibit endotoxin-induced cachectin/tumor necrosis factor synthesis at separate points in the signaling pathway. J Exp Med. 1990 Jul 1;172(1):391–394. [PMC free article] [PubMed]
  • Kovach NL, Lindgren CG, Fefer A, Thompson JA, Yednock T, Harlan JM. Pentoxifylline inhibits integrin-mediated adherence of interleukin-2- activated human peripheral blood lymphocytes to human umbilical vein endothelial cells, matrix components, and cultured tumor cells. Blood. 1994 Oct 1;84(7):2234–2242. [PubMed]
  • Summers RW, Switz DM, Sessions JT, Jr, Becktel JM, Best WR, Kern F, Jr, Singleton JW. National Cooperative Crohn's Disease Study: results of drug treatment. Gastroenterology. 1979 Oct;77(4 Pt 2):847–869. [PubMed]
  • Malchow H, Ewe K, Brandes JW, Goebell H, Ehms H, Sommer H, Jesdinsky H. European Cooperative Crohn's Disease Study (ECCDS): results of drug treatment. Gastroenterology. 1984 Feb;86(2):249–266. [PubMed]
  • Robinson M, Hanauer S, Hoop R, Zbrozek A, Wilkinson C. Mesalamine capsules enhance the quality of life for patients with ulcerative colitis. Aliment Pharmacol Ther. 1994 Feb;8(1):27–34. [PubMed]
  • Mary JY, Modigliani R. Development and validation of an endoscopic index of the severity for Crohn's disease: a prospective multicentre study. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). Gut. 1989 Jul;30(7):983–989. [PMC free article] [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. [PubMed]
  • Dinarello CA. Interleukin-1 and tumor necrosis factor and their naturally occurring antagonists during hemodialysis. Kidney Int Suppl. 1992 Oct;38:S68–S77. [PubMed]
  • Kriegler M, Perez C, DeFay K, Albert I, Lu SD. A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell. 1988 Apr 8;53(1):45–53. [PubMed]
  • Scallon BJ, Moore MA, Trinh H, Knight DM, Ghrayeb J. Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions. Cytokine. 1995 Apr;7(3):251–259. [PubMed]
  • Todorov P, Cariuk P, McDevitt T, Coles B, Fearon K, Tisdale M. Characterization of a cancer cachectic factor. Nature. 1996 Feb 22;379(6567):739–742. [PubMed]

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