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Published in: Digestive Diseases and Sciences 6/2007

01-06-2007 | Original Article

Adacolumn Selective Leukocyte Adsorption Apheresis in Patients with Active Ulcerative Colitis: Clinical Efficacy, Effects on Plasma IL-8, and Expression of Toll-like Receptor 2 on Granulocytes

Authors: Hiroshi Aoki, Kentaro Nakamura, Yasushi Yoshimatsu, Yukiko Tsuda, Masaki Irie, Katsuyuki Fukuda, Nobuo Hosoe, Nobuo Takada, Koji Shirai, Yasuo Suzuki

Published in: Digestive Diseases and Sciences | Issue 6/2007

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Abstract

Adacolumn selective granulocyte and monocyte apheresis (GMA) depletes activated leukocytes in patients with ulcerative colitis (UC). However, this per se cannot fully explain the efficacy of GMA. We have investigated the effects of GMA on the expression of toll-like receptors (TLRs) and plasma interleukin-8 (IL-8). Twenty-two patients with clinical activity index (CAI) of 5–17, 15 with total colitis and 7 with left-sided colitis, were included. Each patient could receive up to 10 GMA sessions, at 1 or 2 sessions per week. GMA was added to the patients’ ongoing medication following a relapse or worsening UC, but no additional medication was given. Further, at entry and pre-GMA, blood samples were taken for full blood cell count, expression of TLRs on leukocytes, and plasma IL-8. Seventy-five percent of patients achieved remission after the 10th session (CAI, ≤4; P < 0.005) and there was a marked fall in C-reactive protein (P < 0.01), plasma IL-8 (P < 0.001), and granulocytes (P < 0.05) but an increase in lymphocytes (P < 0.05). The expression of TLR2 on granulocytes was down-modulated (P < 0.05) together with suppression of inflammatory cytokines produced by peripheral blood leukocytes. In conclusion, GMA appears to be an effective adjunct therapy to induce remission in the majority of patients, who are then spared from excess drug therapy. The procedure is associated with sustained immunomodulation. Control studies should strengthen these findings.
Literature
1.
go back to reference Shimoyama T, Sawada K, Hiwatashi N (2001) Safety and efficacy of granulocytes and monocyte adsorption apheresis in patients with active ulcerative colitis: a multicenter study. J Clin Apher 16:1–9PubMedCrossRef Shimoyama T, Sawada K, Hiwatashi N (2001) Safety and efficacy of granulocytes and monocyte adsorption apheresis in patients with active ulcerative colitis: a multicenter study. J Clin Apher 16:1–9PubMedCrossRef
2.
go back to reference Saniabadi AR, Hanai H, Lofberg R (2003) Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher Dial 7:48–59PubMedCrossRef Saniabadi AR, Hanai H, Lofberg R (2003) Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher Dial 7:48–59PubMedCrossRef
3.
go back to reference Hanai H, Watanabe F, Takeuchi K, et al. (2003) Leukcocyte adsorptive apheresis for the treatment of active ulcerative colitis:a prospective uncontrolled pilot study. Clin Gastroenterol Hepatol 1:28–35PubMedCrossRef Hanai H, Watanabe F, Takeuchi K, et al. (2003) Leukcocyte adsorptive apheresis for the treatment of active ulcerative colitis:a prospective uncontrolled pilot study. Clin Gastroenterol Hepatol 1:28–35PubMedCrossRef
4.
go back to reference Kashiwagi N, Sugimura K, Koiwai H, Saniabadi A (2002) Immunomodulatory effects of granulocyte and monocyte adsorption apheresis as a treatment for patients with ulcerative colitis. Dig. Dis Sci 6:1334–1341CrossRef Kashiwagi N, Sugimura K, Koiwai H, Saniabadi A (2002) Immunomodulatory effects of granulocyte and monocyte adsorption apheresis as a treatment for patients with ulcerative colitis. Dig. Dis Sci 6:1334–1341CrossRef
5.
go back to reference Suzuki Y, Yoshimura N, Saniabadi AR, Saito Y (2004) Selective granulocytes and monocyte adsorptive apheresis as a first-line treatment for steroid naïve patients with active ulcerative colitis:a prospective uncontrolled study. Dig Dis Sci 49:565–571PubMedCrossRef Suzuki Y, Yoshimura N, Saniabadi AR, Saito Y (2004) Selective granulocytes and monocyte adsorptive apheresis as a first-line treatment for steroid naïve patients with active ulcerative colitis:a prospective uncontrolled study. Dig Dis Sci 49:565–571PubMedCrossRef
6.
go back to reference Saniabadi AR, Hanai H, Suzuki Y, Bjarnason I, Lofberg R (2005) Adacolumn for selective leukocytapheresis as a non-pharmacological treatment for patients with disorders of the immune system:an adjunct or an alternative to drug therapy? J Clin Apher 20:171–184PubMedCrossRef Saniabadi AR, Hanai H, Suzuki Y, Bjarnason I, Lofberg R (2005) Adacolumn for selective leukocytapheresis as a non-pharmacological treatment for patients with disorders of the immune system:an adjunct or an alternative to drug therapy? J Clin Apher 20:171–184PubMedCrossRef
7.
go back to reference Kanke K, Nakano M, Hiraishi H (2004) Evaluation of granulocyte/monocyte apheresis therapy for active ulcerative colitis. Dig Liv Dis 36:512–518CrossRef Kanke K, Nakano M, Hiraishi H (2004) Evaluation of granulocyte/monocyte apheresis therapy for active ulcerative colitis. Dig Liv Dis 36:512–518CrossRef
8.
go back to reference Naganuma M, Funakoshi S, Sakuraba A, Hibi T (2004) Granulocytapheresis is useful as an alternative therapy in patients with steroid-refractory or -dependent ulcerative colitis. Inflamm Bowel Dis 10:251–257PubMedCrossRef Naganuma M, Funakoshi S, Sakuraba A, Hibi T (2004) Granulocytapheresis is useful as an alternative therapy in patients with steroid-refractory or -dependent ulcerative colitis. Inflamm Bowel Dis 10:251–257PubMedCrossRef
9.
go back to reference Yamamoto T, Umegae S, Kitagawa T (2004) Granulocyte and monocyte adsorptive apheresis in the treatment of active distal ulcerative colitis: a prospective, pilot study. Aliment Pharmacol Ther 20:783–792PubMedCrossRef Yamamoto T, Umegae S, Kitagawa T (2004) Granulocyte and monocyte adsorptive apheresis in the treatment of active distal ulcerative colitis: a prospective, pilot study. Aliment Pharmacol Ther 20:783–792PubMedCrossRef
10.
go back to reference Domenech E, Hinojosa J, Esteve-Comas M, Gassull A, Spanish Group for the Study of Crohn's Disease and Ulcerative Colitis (GETECCU) (2004) Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease: a prospective, open, pilot study. Aliment Pharmacol Ther 20:1347–1352PubMedCrossRef Domenech E, Hinojosa J, Esteve-Comas M, Gassull A, Spanish Group for the Study of Crohn's Disease and Ulcerative Colitis (GETECCU) (2004) Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease: a prospective, open, pilot study. Aliment Pharmacol Ther 20:1347–1352PubMedCrossRef
11.
go back to reference Suzuki Y, Yoshimora N, Saito Y, Saniabadi A (2006) A retrospective search for predictors of clinical response to selective granulocyte and monocyte apheresis in patients with ulcerative colitis. Dig Dis Sci (in press) Suzuki Y, Yoshimora N, Saito Y, Saniabadi A (2006) A retrospective search for predictors of clinical response to selective granulocyte and monocyte apheresis in patients with ulcerative colitis. Dig Dis Sci (in press)
12.
go back to reference McCarthy DA, Rampton DS, Liu Y-C (1991) Peripheral blood neutrophils in inflammatory bowel disease:morphological evidence of in vivo activation in active disease. Clin Exp Immunol 86:489–493PubMedCrossRef McCarthy DA, Rampton DS, Liu Y-C (1991) Peripheral blood neutrophils in inflammatory bowel disease:morphological evidence of in vivo activation in active disease. Clin Exp Immunol 86:489–493PubMedCrossRef
13.
go back to reference Rugtveit J, Brandtzaeg P, Halstensen TS, Fausa O, Scott H (1994) Increased macrophage subsets in inflammatory bowel disease:apparent recruitment from peripheral blood monocytes. Gut 35:669–674PubMed Rugtveit J, Brandtzaeg P, Halstensen TS, Fausa O, Scott H (1994) Increased macrophage subsets in inflammatory bowel disease:apparent recruitment from peripheral blood monocytes. Gut 35:669–674PubMed
14.
go back to reference Meuret G, Bitzi A, Hammer B (1978) Macrophage turnover in Crohn's disease and ulcerative colitis. Gastroenterology 74:501–503PubMed Meuret G, Bitzi A, Hammer B (1978) Macrophage turnover in Crohn's disease and ulcerative colitis. Gastroenterology 74:501–503PubMed
15.
go back to reference Brannigan AE, O’Connell PR, Hurley H (2000) Neutrophil apoptosis is delayed in patients with inflammatory bowel disease. Shock 13:361–366PubMed Brannigan AE, O’Connell PR, Hurley H (2000) Neutrophil apoptosis is delayed in patients with inflammatory bowel disease. Shock 13:361–366PubMed
16.
go back to reference Cassatella MA (1995) The production of cytokines by polymorphonuclear neutrophils. Immunol Today 16:21–26PubMedCrossRef Cassatella MA (1995) The production of cytokines by polymorphonuclear neutrophils. Immunol Today 16:21–26PubMedCrossRef
17.
go back to reference Nikolaus S, Bauditz J, Gionchetti P (1998) Increased secretion of pro-inflammatory cytokines by circulating polymorphonuclear neutrophils and regulation by interleukin-10 during intestinal inflammation. Gut 42:470–476PubMedCrossRef Nikolaus S, Bauditz J, Gionchetti P (1998) Increased secretion of pro-inflammatory cytokines by circulating polymorphonuclear neutrophils and regulation by interleukin-10 during intestinal inflammation. Gut 42:470–476PubMedCrossRef
18.
go back to reference Mahida YR (2000) The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. Inflamm Bowel Dis 6:21–33PubMedCrossRef Mahida YR (2000) The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. Inflamm Bowel Dis 6:21–33PubMedCrossRef
19.
go back to reference Hanauer SB (2006) Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 12:S3–S9PubMedCrossRef Hanauer SB (2006) Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 12:S3–S9PubMedCrossRef
20.
go back to reference Allison MC, Dhillon AP, Lewis WG, Pounder RE, eds (1998) Inflammatory bowel disease. Mosby, London, pp 15–95 Allison MC, Dhillon AP, Lewis WG, Pounder RE, eds (1998) Inflammatory bowel disease. Mosby, London, pp 15–95
21.
go back to reference Tibble JA, Sigthorsson G, Bridger D, Fagerhol MK, Bjarnason I (2000) Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 119:15–22PubMedCrossRef Tibble JA, Sigthorsson G, Bridger D, Fagerhol MK, Bjarnason I (2000) Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 119:15–22PubMedCrossRef
22.
go back to reference Limburg P, David M, Ahlquist A, Sandborn WJ (2000) Faecal calprotectin levels predict colorectal inflammation among patients with chronic diarrhoea referred for colonoscopy. Am J Gastroenterol 95:2831–2837PubMedCrossRef Limburg P, David M, Ahlquist A, Sandborn WJ (2000) Faecal calprotectin levels predict colorectal inflammation among patients with chronic diarrhoea referred for colonoscopy. Am J Gastroenterol 95:2831–2837PubMedCrossRef
23.
go back to reference Hiraishi K, Takeda Y, Shiobara N, Saniabadi A (2003) Studies on the mechanisms of leukocyte adhesion to cellulose acetate beads:an in vitro model to assess the efficacy of cellulose acetate carrier-based granulocyte and monocyte adsorptive apheresis. Ther Apher Dial 7:334–340PubMedCrossRef Hiraishi K, Takeda Y, Shiobara N, Saniabadi A (2003) Studies on the mechanisms of leukocyte adhesion to cellulose acetate beads:an in vitro model to assess the efficacy of cellulose acetate carrier-based granulocyte and monocyte adsorptive apheresis. Ther Apher Dial 7:334–340PubMedCrossRef
24.
go back to reference D’Arrigo C, Candal-Couto JJ, Greer M (1993) Human neutrophil Fc receptor-mediated adhesion under flow: a hallow fiber model of intravascular arrest. Clin Exp Immunol 100:173–179CrossRef D’Arrigo C, Candal-Couto JJ, Greer M (1993) Human neutrophil Fc receptor-mediated adhesion under flow: a hallow fiber model of intravascular arrest. Clin Exp Immunol 100:173–179CrossRef
25.
go back to reference Pierik M, Joossens S, Van Steen K (2006) Toll-like receptor-1, -2, and -6 polymorphisms influence disease extension in inflammatory bowel diseases. Inflamm Bowel Dis 12:1–8PubMedCrossRef Pierik M, Joossens S, Van Steen K (2006) Toll-like receptor-1, -2, and -6 polymorphisms influence disease extension in inflammatory bowel diseases. Inflamm Bowel Dis 12:1–8PubMedCrossRef
26.
go back to reference Rachmilewitz D (on behalf of an international study group) (1989) Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomized trial. Br Med J 298:82–86 Rachmilewitz D (on behalf of an international study group) (1989) Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomized trial. Br Med J 298:82–86
27.
go back to reference Kurt-Jones EA, Whitney MC, Padgett A, Gosselin K, Newburger PE, Finberg RW (2002) Role of toll-like receptor 2 (TLR2) in neutrophil activation: GM-CSF enhances TLR2 expression and TLR2-mediated interleukin 8 responses in neutrophils. Blood 100:1860–1868PubMed Kurt-Jones EA, Whitney MC, Padgett A, Gosselin K, Newburger PE, Finberg RW (2002) Role of toll-like receptor 2 (TLR2) in neutrophil activation: GM-CSF enhances TLR2 expression and TLR2-mediated interleukin 8 responses in neutrophils. Blood 100:1860–1868PubMed
28.
go back to reference Swaak AJ, van den Brink HG, Aarden LA (1997) Cytokine production in whole blood cell cultures of patients with rheumatoid arthritis. Ann Rheum Dis 56:693–695PubMed Swaak AJ, van den Brink HG, Aarden LA (1997) Cytokine production in whole blood cell cultures of patients with rheumatoid arthritis. Ann Rheum Dis 56:693–695PubMed
29.
go back to reference Lerebours E, Bussel A, Modigliani R, Bastit D, Florent C, Rabian C (1994) Treatment of Crohn's disease by lymphocyte apheresis:a randomized controlled trial. Gastroenterology 107:357–361PubMed Lerebours E, Bussel A, Modigliani R, Bastit D, Florent C, Rabian C (1994) Treatment of Crohn's disease by lymphocyte apheresis:a randomized controlled trial. Gastroenterology 107:357–361PubMed
30.
go back to reference Isaacs KL, Lewis JD, Sandborn WJ, Sands BE, Targan SR (2005) State of the art:IBD therapy and clinical trials in IBD. Inflamm Bowel Dis 11:S3–S12PubMedCrossRef Isaacs KL, Lewis JD, Sandborn WJ, Sands BE, Targan SR (2005) State of the art:IBD therapy and clinical trials in IBD. Inflamm Bowel Dis 11:S3–S12PubMedCrossRef
31.
go back to reference Barrat FJ, Meeker T, Gregorio J, Chan JH, Uematsu S, Akira S, Chang B, Duramad O, Coffman RL (2005) Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J Exp Med 202:1131–1139PubMedCrossRef Barrat FJ, Meeker T, Gregorio J, Chan JH, Uematsu S, Akira S, Chang B, Duramad O, Coffman RL (2005) Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J Exp Med 202:1131–1139PubMedCrossRef
32.
go back to reference Kanai K, Watanabe M (2005) Clinical application of human CD4+CD25+ regulatory T cells for the treatment of inflammatory bowel diseases. Expert Opin Biol Ther 5:451–462PubMedCrossRef Kanai K, Watanabe M (2005) Clinical application of human CD4+CD25+ regulatory T cells for the treatment of inflammatory bowel diseases. Expert Opin Biol Ther 5:451–462PubMedCrossRef
33.
go back to reference King C, Ilic A, Koelsch K, Sarvetnick N (2004) Homeostatic expansion of T cells during immune insufficiency generates autoimmunity. Cell 117:265–277PubMedCrossRef King C, Ilic A, Koelsch K, Sarvetnick N (2004) Homeostatic expansion of T cells during immune insufficiency generates autoimmunity. Cell 117:265–277PubMedCrossRef
34.
go back to reference Sleasman JW (1996) The association between immunodeficiency and the development of autoimmune disease. Adv Dent Res 10:57–61PubMedCrossRef Sleasman JW (1996) The association between immunodeficiency and the development of autoimmune disease. Adv Dent Res 10:57–61PubMedCrossRef
35.
go back to reference Banerjee D, Liou HC, Sen R (2005) c-Rel-dependent priming of naive T Cells by inflammatory cytokines. Immunity 23:445–458PubMedCrossRef Banerjee D, Liou HC, Sen R (2005) c-Rel-dependent priming of naive T Cells by inflammatory cytokines. Immunity 23:445–458PubMedCrossRef
36.
go back to reference Hanai H, Watanabe F, Saniabadi A, Matsushita I, Takeuchi K, Iida T (2002) Therapeutic efficacy of granulocyte and monocyte adsorption apheresis in severe active ulcerative colitis. Dig Dis Sci 47:2349–2353PubMedCrossRef Hanai H, Watanabe F, Saniabadi A, Matsushita I, Takeuchi K, Iida T (2002) Therapeutic efficacy of granulocyte and monocyte adsorption apheresis in severe active ulcerative colitis. Dig Dis Sci 47:2349–2353PubMedCrossRef
37.
go back to reference Dionne S, D’Agata ID, Hiscott J, Vanounou T, Seidman EG (1998) Colonic explant production of IL-1 and its receptor antagonist is imbalanced in inflammatory bowel disease (IBD). Clin Exp Immunol 112:435–442PubMedCrossRef Dionne S, D’Agata ID, Hiscott J, Vanounou T, Seidman EG (1998) Colonic explant production of IL-1 and its receptor antagonist is imbalanced in inflammatory bowel disease (IBD). Clin Exp Immunol 112:435–442PubMedCrossRef
Metadata
Title
Adacolumn Selective Leukocyte Adsorption Apheresis in Patients with Active Ulcerative Colitis: Clinical Efficacy, Effects on Plasma IL-8, and Expression of Toll-like Receptor 2 on Granulocytes
Authors
Hiroshi Aoki
Kentaro Nakamura
Yasushi Yoshimatsu
Yukiko Tsuda
Masaki Irie
Katsuyuki Fukuda
Nobuo Hosoe
Nobuo Takada
Koji Shirai
Yasuo Suzuki
Publication date
01-06-2007
Published in
Digestive Diseases and Sciences / Issue 6/2007
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-006-9406-8

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