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International Journal of Hematology
Published in: International Journal of Hematology 5/2011

01-05-2011 | Progress in Hematology

Implications of TNF-α in the pathogenesis and management of GVHD

Author: John E. Levine

Published in: International Journal of Hematology | Issue 5/2011

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Abstract

Clinical graft-versus-host disease (GVHD) symptoms are the result of a complex set of interactions between cellular and soluble factors. One of the key soluble factors is the proinflammatory cytokine, TNF-α, which participates in the initiating events that culminate in GVHD as well as amplifies the disease process once established. The importance of TNF-α in this process has been supported by a series of clinical experiments demonstrating strong correlation between TNF receptor-1 levels and GVHD. TNF-α has both indirect effects, through activating and proliferation pathways of T cells, the main cellular effector of GVHD, and direct effects leading to apoptosis, on GVHD target tissues. Accordingly, TNF-α has been used as a therapeutic target in experimental GVHD prevention and treatment strategies with promising clinical results. TNF-α can be pharmacologically inhibited using soluble TNF receptors or monoclonal antibodies. The optimal dosing and duration of TNF inhibition to prevent or treat GVHD remains under investigation.
Literature
1.
Antin JH, Ferrara JL. Cytokine dysregulation and acute graft-versus-host disease. Blood. 1992;80:2964–8.PubMed
2.
3.
4.
Xun CQ, Thompson JS, Jennings CD, Brown SA, Widmer MB. Effect of total body irradiation, busulfan-cyclophosphamide, or cyclophosphamide conditioning on inflammatory cytokine release and development of acute and chronic graft-versus-host disease in H-2-incompatible transplanted SCID mice. Blood. 1994;83:2360–7.PubMed
5.
Hill GR, Ferrara JL. The primacy of the gastrointestinal tract as a target organ of acute graft-versus-host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation. Blood. 2000;95:2754–9.PubMed
6.
Hill GR, Crawford JM, Cooke KR, Brinson YS, Pan L, Ferrara JL. Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines. Blood. 1997;90:3204–13.PubMed
7.
Bollyky PL, Evanko SP, Wu RP, et al. Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse. Cell Mol Immunol. 2010;7:211–20.CrossRefPubMedPubMedCentral
8.
Ratanatharathorn V, Nash RA, Przepiorka D, et al. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood. 1998;92:2303–14.PubMed
9.
Nash RA, Antin JH, Karanes C, et al. Phase III study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood. 2000;96:2062–8.PubMed
10.
Lee SJ, Zahrieh D, Agura E, et al. Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial. Blood. 2004;104:1559–64.CrossRefPubMed
11.
Zeiser R, Nguyen VH, Beilhack A, et al. Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood. 2006;108:390–9.CrossRefPubMedPubMedCentral
12.
Welniak LA, Blazar BR, Murphy WJ. Immunobiology of allogeneic hematopoietic stem cell transplantation. Annu Rev Immunol. 2007;25:139–70.CrossRefPubMed
13.
14.
Cooke KR, Hill GR, Crawford JM, et al. Tumor necrosis factor- alpha production to lipopolysaccharide stimulation by donor cells predicts the severity of experimental acute graft-versus-host disease. J Clin Invest. 1998;102:1882–91.CrossRefPubMedPubMedCentral
15.
Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol. 2004;5:987–95.CrossRefPubMed
16.
Brown GR, Lindberg G, Meddings J, Silva M, Beutler B, Thiele D. Tumor necrosis factor inhibitor ameliorates murine intestinal graft-versus-host disease. Gastroent. 1999;116:593–601.CrossRef
17.
Stuber E, Buschenfeld A, von Freier A, Arendt T, Folsch UR. Intestinal crypt cell apoptosis in murine acute graft versus host disease is mediated by tumour necrosis factor alpha and not by the FasL–Fas interaction: effect of pentoxifylline on the development of mucosal atrophy. Gut. 1999;45:229–35.CrossRefPubMedPubMedCentral
18.
Holler E, Kolb HJ, Moller A, et al. Increased serum levels of tumor necrosis factor alpha precede major complications of bone marrow transplantation. Blood. 1990;75:1011–6.PubMed
19.
Choi SW, Kitko CL, Braun T, et al. Change in plasma tumor necrosis factor receptor 1 levels in the first week after myeloablative allogeneic transplantation correlates with severity and incidence of GVHD and survival. Blood. 2008;112:1539–42.CrossRefPubMedPubMedCentral
20.
Kitko CL, Paczesny S, Yanik G, et al. Plasma elevations of tumor necrosis factor-receptor-1 at day 7 postallogeneic transplant correlate with graft-versus-host disease severity and overall survival in pediatric patients. Biol Blood Marrow Transpl. 2008;14:759–65.CrossRef
21.
Vandenabeele P, Declercq W, Beyaert R, Fiers W. Two tumour necrosis factor receptors: structure and function. Trends Cell Biol. 1995;5:392–9.CrossRefPubMed
22.
Levine JE, Uberti JP, Ayash L, et al. Lowered-intensity preparative regimen for allogeneic stem cell transplantation delays acute graft-versus-host disease but does not improve outcome for advanced hematologic malignancy. Biol Blood Marrow Transpl. 2003;9:189–97.CrossRef
23.
Mielcarek M, Martin PJ, Leisenring W, et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood. 2003;102:756–62.CrossRefPubMed
24.
Couriel DR, Saliba RM, Giralt S, et al. Acute and chronic graft-versus-host disease after ablative and nonmyeloablative conditioning for allogeneic hematopoietic transplantation. Biol Blood Marrow Transplant. 2004;10:178–85.CrossRefPubMed
25.
Willems E, Humblet-Baron S, Dengis O, Seidel L, Beguin Y, Baron F. Elevations of tumor necrosis factor receptor 1 at day 7 and acute graft-versus-host disease after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. Bone Marrow Transplant. 2010;45:1442–8.CrossRefPubMed
26.
Fowler DH, Foley J, Whit-Shan Hou J, et al. Clinical “cytokine storm” as revealed by monocyte intracellular flow cytometry: correlation of tumor necrosis factor alpha with severe gut graft-versus-host disease. Clin Gastroenterol Hepatol. 2004;2:237–45.CrossRefPubMed
27.
Ritchie D, Seconi J, Wood C, Walton J, Watt V. Prospective monitoring of tumor necrosis factor alpha and interferon gamma to predict the onset of acute and chronic graft-versus-host disease after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2005;11:706–12.CrossRefPubMed
28.
29.
Paczesny S, Braun T, Levine JE, et al. Elafin is a biomarker of graft-versus-host disease of the skin. Sci Transl Med. 2010;2:50–7.CrossRef
30.
Hamadani M, Hofmeister CC, Jansak B, et al. Addition of infliximab to standard acute graft-versus-host disease prophylaxis following allogeneic peripheral blood cell transplantation. Biol Blood Marrow Transplant. 2008;14:783–9.CrossRefPubMedPubMedCentral
31.
Levine JE, Paczesny S, Mineishi S, et al. Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host disease. Blood. 2008;111:2470–5.CrossRefPubMedPubMedCentral
32.
Imamura M, Hashino S, Kobayashi H, Kubayashi S, Hirano S. Serum cytokine levels in bone marrow transplantation: Synergistic interaction of interleukin-6, interferon-γ, and tumor necrosis factor-α in graft-versus-host disease. Bone Marrow Transpl. 1994;13:745–51.
33.
Ehlers S. Tumor necrosis factor and its blockade in granulomatous infections: differential modes of action of infliximab and etanercept? Clin Infect Dis. 2005;41(Suppl 3):S199–203.CrossRefPubMed
34.
Couriel D, Saliba R, Hicks K, et al. Tumor necrosis factor-alpha blockade for the treatment of acute GVHD. Blood. 2004;104:649–54.CrossRefPubMed
35.
Marty FM, Lee SJ, Fahey MM, et al. Infliximab use in patients with severe graft-versus-host disease and other emerging risk factors of non-Candida invasive fungal infections in allogeneic hematopoietic stem cell transplant recipients: a cohort study. Blood. 2003;102:2768–76.CrossRefPubMed
36.
Alousi AM, Weisdorf DJ, Logan BR, et al. Etanercept, mycophenolate, denileukin or pentostatin plus corticosteroids for acute graft vs. host disease: a randomized phase II trial from the BMT CTN. Blood. 2009;114:511–7.CrossRefPubMedPubMedCentral
37.
MacMillan ML, Weisdorf DJ, Wagner JE, et al. Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems. Biol Blood Marrow Transpl. 2002;8:387–94.CrossRef
38.
Couriel DR, Saliba R, de Lima M, et al. A phase III study of infliximab and corticosteroids for the initial treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant. 2009;15:1555–62.CrossRefPubMedPubMedCentral
39.
Busca A, Locatelli F, Marmont F, Ceretto C, Falda M. Recombinant human soluble tumor necrosis factor receptor fusion protein as treatment for steroid refractory graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2007;82:45–52.CrossRefPubMed
40.
Sleight BS, Chan KW, Braun TM, Serrano A, Gilman AL. Infliximab for GVHD therapy in children. Bone Marrow Transplant. 2007;40:473–80.CrossRefPubMed
41.
Patriarca F, Sperotto A, Damiani D, et al. Infliximab treatment for steroid-refractory acute graft-versus-host disease. Haematologica. 2004;89:1352–9.PubMed
42.
Jacobsohn DA, Hallick J, Anders V, McMillan S, Morris L, Vogelsang GB. Infliximab for steroid-refractory acute GVHD: a case series. Am J Hematol. 2003;74:119–24.CrossRefPubMed
Metadata
Title
Implications of TNF-α in the pathogenesis and management of GVHD
Author
John E. Levine
Publication date
01-05-2011
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 5/2011
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-011-0803-1

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