Interleukin 10 gene transfer prevents experimental colitis in rats.
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Journal: 2000/March - Gut
ISSN: 0017-5749
PUBMED: 10673295
Abstract:
BACKGROUND
The development of colitis in interleukin 10 (IL-10) deficient mice, together with the known anti-inflammatory and immunomodulatory properties of this cytokine have prompted consideration of IL-10 as a treatment for inflammatory bowel disease (IBD). However, studies using hrIL-10 in IBD models have yielded inconsistent results.
OBJECTIVE
To examine the therapeutic potential of overexpressing the IL-10 gene before and after the induction of experimental colitis in rats.
METHODS
Gene transfer was achieved by intraperitoneal injection of non-replicating human type 5 adenovirus bearing the IL-10 gene, either 24 hours before or one hour after intrarectal administration of dinitrobenzene sulphonic acid in rats. Colonic damage and inflammation was assessed macroscopically and by measuring myeloperoxidase activity and leukotriene B4 concentrations.
RESULTS
Gene transfer increased IL-10 protein in serum for up to six days. IL-10 gene transfer prior to colitis improved colitis macroscopically and histologically, and significantly reduced colonic myeloperoxidase activity and leukotriene B4 concentrations. In contrast, IL-10 gene transfer after the onset of colitis had no beneficial effect.
CONCLUSIONS
Gene therapy using an adenovirus-IL-10 construct was successful in preventing but not in reversing experimental colitis in the rat.
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Gut 46(3): 344-349
PMID: 10673295

Interleukin 10 gene transfer prevents experimental colitis in rats

Abstract

BACKGROUND—The development of colitis in interleukin 10 (IL-10) deficient mice, together with the known anti-inflammatory and immunomodulatory properties of this cytokine have prompted consideration of IL-10 as a treatment for inflammatory bowel disease (IBD). However, studies using hrIL-10 in IBD models have yielded inconsistent results.
AIMS—To examine the therapeutic potential of overexpressing the IL-10 gene before and after the induction of experimental colitis in rats.
METHODS—Gene transfer was achieved by intraperitoneal injection of non-replicating human type 5 adenovirus bearing the IL-10 gene, either 24 hours before or one hour after intrarectal administration of dinitrobenzene sulphonic acid in rats. Colonic damage and inflammation was assessed macroscopically and by measuring myeloperoxidase activity and leukotriene B4 concentrations.
RESULTS—Gene transfer increased IL-10 protein in serum for up to six days. IL-10 gene transfer prior to colitis improved colitis macroscopically and histologically, and significantly reduced colonic myeloperoxidase activity and leukotriene B4 concentrations. In contrast, IL-10 gene transfer after the onset of colitis had no beneficial effect.
CONCLUSIONS—Gene therapy using an adenovirus-IL-10 construct was successful in preventing but not in reversing experimental colitis in the rat.


Keywords: gene therapy; colitis; interleukin 10; adenovirus vector; leukotrienes; inflammatory bowel disease; maintenance therapy

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Selected References

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  • Sartor RB. Cytokines in intestinal inflammation: pathophysiological and clinical considerations. Gastroenterology. 1994 Feb;106(2):533–539. [PubMed] [Google Scholar]
  • 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] [Google Scholar]
  • Hogaboam CM, Vallance BA, Kumar A, Addison CL, Graham FL, Gauldie J, Collins SM. Therapeutic effects of interleukin-4 gene transfer in experimental inflammatory bowel disease. J Clin Invest. 1997 Dec 1;100(11):2766–2776.[PMC free article] [PubMed] [Google Scholar]
  • de Vries JE. Immunosuppressive and anti-inflammatory properties of interleukin 10. Ann Med. 1995 Oct;27(5):537–541. [PubMed] [Google Scholar]
  • Kühn R, Löhler J, Rennick D, Rajewsky K, Müller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993 Oct 22;75(2):263–274. [PubMed] [Google Scholar]
  • Berg DJ, Davidson N, Kühn R, Müller W, Menon S, Holland G, Thompson-Snipes L, Leach MW, Rennick D. Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J Clin Invest. 1996 Aug 15;98(4):1010–1020.[PMC free article] [PubMed] [Google Scholar]
  • Schreiber S, Heinig T, Thiele HG, Raedler A. Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease. Gastroenterology. 1995 May;108(5):1434–1444. [PubMed] [Google Scholar]
  • van Deventer SJ, Elson CO, Fedorak RN. Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn's disease. Crohn's Disease Study Group. Gastroenterology. 1997 Aug;113(2):383–389. [PubMed] [Google Scholar]
  • Herfarth HH, Mohanty SP, Rath HC, Tonkonogy S, Sartor RB. Interleukin 10 suppresses experimental chronic, granulomatous inflammation induced by bacterial cell wall polymers. Gut. 1996 Dec;39(6):836–845.[PMC free article] [PubMed] [Google Scholar]
  • Ribbons KA, Thompson JH, Liu X, Pennline K, Clark DA, Miller MJ. Anti-inflammatory properties of interleukin-10 administration in hapten-induced colitis. Eur J Pharmacol. 1997 Apr 4;323(2-3):245–254. [PubMed] [Google Scholar]
  • Chernoff AE, Granowitz EV, Shapiro L, Vannier E, Lonnemann G, Angel JB, Kennedy JS, Rabson AR, Wolff SM, Dinarello CA. A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses. J Immunol. 1995 May 15;154(10):5492–5499. [PubMed] [Google Scholar]
  • Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology. 1989 Mar;96(3):795–803. [PubMed] [Google Scholar]
  • Wallace JL, Le T, Carter L, Appleyard CB, Beck PL. Hapten-induced chronic colitis in the rat: alternatives to trinitrobenzene sulfonic acid. J Pharmacol Toxicol Methods. 1995 Aug;33(4):237–239. [PubMed] [Google Scholar]
  • Xing Z, Ohkawara Y, Jordana M, Graham FL, Gauldie J. Adenoviral vector-mediated interleukin-10 expression in vivo: intramuscular gene transfer inhibits cytokine responses in endotoxemia. Gene Ther. 1997 Feb;4(2):140–149. [PubMed] [Google Scholar]
  • Marshall JS, Leal-Berumen I, Nielsen L, Glibetic M, Jordana M. Interleukin (IL)-10 inhibits long-term IL-6 production but not preformed mediator release from rat peritoneal mast cells. J Clin Invest. 1996 Feb 15;97(4):1122–1128.[PMC free article] [PubMed] [Google Scholar]
  • de Wet JR, Wood KV, DeLuca M, Helinski DR, Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737.[PMC free article] [PubMed] [Google Scholar]
  • Wallace JL, Keenan CM. An orally active inhibitor of leukotriene synthesis accelerates healing in a rat model of colitis. Am J Physiol. 1990 Apr;258(4 Pt 1):G527–G534. [PubMed] [Google Scholar]
  • Boughton-Smith NK, Wallace JL, Whittle BJ. Relationship between arachidonic acid metabolism, myeloperoxidase activity and leukocyte infiltration in a rat model of inflammatory bowel disease. Agents Actions. 1988 Aug;25(1-2):115–123. [PubMed] [Google Scholar]
  • Drazan KE, Wu L, Bullington D, Shaked A. Viral IL-10 gene therapy inhibits TNF-alpha and IL-1 beta, not IL-6, in the newborn endotoxemic mouse. J Pediatr Surg. 1996 Mar;31(3):411–414. [PubMed] [Google Scholar]
  • Brown GR, Thiele DL, Silva M, Beutler B. Adenoviral vectors given intravenously to immunocompromised mice yield stable transduction of the colonic epithelium. Gastroenterology. 1997 May;112(5):1586–1594. [PubMed] [Google Scholar]
  • Hamilton TE, McClane SJ, Baldwin S, Burke C, Patel H, Rombeau JL, Raper SE. Efficient adenoviral-mediated murine neonatal small intestinal gene transfer is dependent on alpha(v) integrin expression. J Pediatr Surg. 1997 Dec;32(12):1695–1703. [PubMed] [Google Scholar]
  • Sferra TJ, McNeely D, Johnson PR. Gene transfer to the intestinal tract: a new approach using selective injection of the superior mesenteric artery. Hum Gene Ther. 1997 Apr 10;8(6):681–687. [PubMed] [Google Scholar]
  • Sironi M, Muñoz C, Pollicino T, Siboni A, Sciacca FL, Bernasconi S, Vecchi A, Colotta F, Mantovani A. Divergent effects of interleukin-10 on cytokine production by mononuclear phagocytes and endothelial cells. Eur J Immunol. 1993 Oct;23(10):2692–2695. [PubMed] [Google Scholar]
  • Piedimonte G, Pickles RJ, Lehmann JR, McCarty D, Costa DL, Boucher RC. Replication-deficient adenoviral vector for gene transfer potentiates airway neurogenic inflammation. Am J Respir Cell Mol Biol. 1997 Mar;16(3):250–258. [PubMed] [Google Scholar]
  • Wallace JL, McKnight W, Asfaha S, Liu DY. Reduction of acute and reactivated colitis in rats by an inhibitor of neutrophil activation. Am J Physiol. 1998 May;274(5 Pt 1):G802–G808. [PubMed] [Google Scholar]
  • Iademarco MF, Barks JL, Dean DC. Regulation of vascular cell adhesion molecule-1 expression by IL-4 and TNF-alpha in cultured endothelial cells. J Clin Invest. 1995 Jan;95(1):264–271.[PMC free article] [PubMed] [Google Scholar]
  • Krakauer T. IL-10 inhibits the adhesion of leukocytic cells to IL-1-activated human endothelial cells. Immunol Lett. 1995 Feb;45(1-2):61–65. [PubMed] [Google Scholar]
  • Cassatella MA, Meda L, Bonora S, Ceska M, Constantin G. Interleukin 10 (IL-10) inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes. Evidence for an autocrine role of tumor necrosis factor and IL-1 beta in mediating the production of IL-8 triggered by lipopolysaccharide. J Exp Med. 1993 Dec 1;178(6):2207–2211.[PMC free article] [PubMed] [Google Scholar]
  • Kasama T, Strieter RM, Lukacs NW, Burdick MD, Kunkel SL. Regulation of neutrophil-derived chemokine expression by IL-10. J Immunol. 1994 Apr 1;152(7):3559–3569. [PubMed] [Google Scholar]
  • Keel M, Ungethüm U, Steckholzer U, Niederer E, Hartung T, Trentz O, Ertel W. Interleukin-10 counterregulates proinflammatory cytokine-induced inhibition of neutrophil apoptosis during severe sepsis. Blood. 1997 Nov 1;90(9):3356–3363. [PubMed] [Google Scholar]
  • Wallace JL, MacNaughton WK, Morris GP, Beck PL. Inhibition of leukotriene synthesis markedly accelerates healing in a rat model of inflammatory bowel disease. Gastroenterology. 1989 Jan;96(1):29–36. [PubMed] [Google Scholar]
  • Macdonald TT. Viral vectors expressing immunoregulatory cytokines to treat inflammatory bowel disease. Gut. 1998 Apr;42(4):460–461.[PMC free article] [PubMed] [Google Scholar]
  • During MJ, Xu R, Young D, Kaplitt MG, Sherwin RS, Leone P. Peroral gene therapy of lactose intolerance using an adeno-associated virus vector. Nat Med. 1998 Oct;4(10):1131–1135. [PubMed] [Google Scholar]
The Intestinal Disease Research Program, Division of Gastroenterology, Departments of Medicine and Pathology, McMaster University Faculty of Health Sciences, Hamilton Health Sciences Corporation, Hamilton, Ontario, Canada.
The Intestinal Disease Research Program, Division of Gastroenterology, Departments of Medicine and Pathology, McMaster University Faculty of Health Sciences, Hamilton Health Sciences Corporation, Hamilton, Ontario, Canada.
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Abstract

BACKGROUND—The development of colitis in interleukin 10 (IL-10) deficient mice, together with the known anti-inflammatory and immunomodulatory properties of this cytokine have prompted consideration of IL-10 as a treatment for inflammatory bowel disease (IBD). However, studies using hrIL-10 in IBD models have yielded inconsistent results.
AIMS—To examine the therapeutic potential of overexpressing the IL-10 gene before and after the induction of experimental colitis in rats.
METHODS—Gene transfer was achieved by intraperitoneal injection of non-replicating human type 5 adenovirus bearing the IL-10 gene, either 24 hours before or one hour after intrarectal administration of dinitrobenzene sulphonic acid in rats. Colonic damage and inflammation was assessed macroscopically and by measuring myeloperoxidase activity and leukotriene B4 concentrations.
RESULTS—Gene transfer increased IL-10 protein in serum for up to six days. IL-10 gene transfer prior to colitis improved colitis macroscopically and histologically, and significantly reduced colonic myeloperoxidase activity and leukotriene B4 concentrations. In contrast, IL-10 gene transfer after the onset of colitis had no beneficial effect.
CONCLUSIONS—Gene therapy using an adenovirus-IL-10 construct was successful in preventing but not in reversing experimental colitis in the rat.


Keywords: gene therapy; colitis; interleukin 10; adenovirus vector; leukotrienes; inflammatory bowel disease; maintenance therapy

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