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Cytokine dysregulation and acute graft-versus-host disease
JH Antin and JL Ferrara
Division of Hematology-Oncology, Brigham and Women's Hospital, Boston, MA
02115.
We suggest that acute GVHD after marrow transplantation reflects (1) host
injury due to the conditioning regimen followed by the production of
inflammatory cytokines; (2) stimulation of mature donor T cells in the
milieu of increased cell surface expression of leukocyte adhesion molecules
and HLA molecules, followed by the autocrine production of IL- 2; and,
finally, (3) recruitment and activation of additional mononuclear effector
cells from donor marrow progenitors, which produce additional inflammatory
cytokines, thus sustaining the response. The second step is critical for
the amplification of the systemic inflammatory response, and it is absence
in autologous, syngeneic, and T-cell-depleted transplants. These T cells
may also contribute to the inflammatory cytokine network. Acute GVHD can
occur in the absence of primary tissue injury in such settings as
transfusion-related GVHD; however, it is likely that a greater HLA
disparity between donor and host is required. We propose that inflammatory
cytokine production is the final common pathway of acute GVHD. If this
model is correct, control of cytokine dysregulation at any of several
points should control GVHD. Further studies of GVHD and investigations of
cytokine antagonists (eg, IL-4 or IL-10) or combinations of antagonists
such as IL-1ra and soluble TNF receptor or pentoxifylline will allow us to
determine the validity of this hypothesis.
Volume 80,
Issue 12,
pp. 2964-2968,
12/15/1992
Copyright © 1992 by The American Society of Hematology
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October 15, 2007;
110(8):
2803 - 2810.
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|
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|
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|
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109(10):
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|
|
|
|
|
|
|
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Blood,
May 1, 2007;
109(9):
4089 - 4096.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
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November 1, 2006;
27(10):
2179 - 2190.
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|
|
|
|
|
|
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Biological and biomaterial approaches for improved islet transplantation.
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June 1, 2006;
58(2):
194 - 243.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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107(8):
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|
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107(5):
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|
|
|
|
|
|
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106(12):
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|
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|
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G. Socié
Graft-versus-host disease--from the bench to the bedside?
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September 29, 2005;
353(13):
1396 - 1397.
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|
|
|
|
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|
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|
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|
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|
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|
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|
|
|
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|
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|
|
|
|
|
|
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|
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|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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[Abstract]
[Full Text]
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|
|
|
|
|
|
|
G. Socie, J.-Y. Mary, M. Lemann, M. Daneshpouy, P. Guardiola, V. Meignin, L. Ades, H. Esperou, P. Ribaud, A. Devergie, et al.
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103(1):
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[Abstract]
[Full Text]
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|
|
|
|
|
|
|
R. S. van Rijn, E. R. Simonetti, A. Hagenbeek, M. C. H. Hogenes, R. A. de Weger, M. R. Canninga-van Dijk, K. Weijer, H. Spits, G. Storm, L. van Bloois, et al.
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October 1, 2003;
102(7):
2522 - 2531.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. Billiau, S. Fevery, O. Rutgeerts, W. Landuyt, and M. Waer
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740 - 748.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Dybedal, L. Yang, D. Bryder, I. Aastrand-Grundstrom, K. Leandersson, and S. E. W. Jacobsen
Human reconstituting hematopoietic stem cells up-regulate Fas expression upon active cell cycling but remain resistant to Fas-induced suppression
Blood,
July 1, 2003;
102(1):
118 - 126.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Reddy, T. Teshima, G. Hildebrandt, D. L. Williams, C. Liu, K. R. Cooke, and J. L.M. Ferrara
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Blood,
April 1, 2003;
101(7):
2877 - 2885.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. R. Drobyski, M. Gendelman, S. Vodanovic-Jankovic, and J. Gorski
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J. Immunol.,
March 15, 2003;
170(6):
3046 - 3053.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Liu, J. G. Heuer, S. Na, E. Galbreath, T. Zhang, D. D. Yang, A. Glasebrook, and H. Y. Song
Accelerated Onset and Increased Severity of Acute Graft-Versus-Host Disease Following Adoptive Transfer of DR6-Deficient T Cells
J. Immunol.,
October 1, 2002;
169(7):
3993 - 3998.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. Billiau, S. Fevery, O. Rutgeerts, W. Landuyt, and M. Waer
Crucial role of timing of donor lymphocyte infusion in generating dissociated graft-versus-host and graft-versus-leukemia responses in mice receiving allogeneic bone marrow transplants
Blood,
August 13, 2002;
100(5):
1894 - 1902.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. R. Drobyski, R. Komorowski, B. Logan, and M. Gendelman
Role of the Passive Apoptotic Pathway in Graft-Versus-Host Disease
J. Immunol.,
August 1, 2002;
169(3):
1626 - 1633.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. A. Tabbara, K. Zimmerman, C. Morgan, and Z. Nahleh
Allogeneic Hematopoietic Stem Cell Transplantation: Complications and Results
Arch Intern Med,
July 22, 2002;
162(14):
1558 - 1566.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hayashi, W. H. Peranteau, A. F. Shaaban, and A. W. Flake
Complete allogeneic hematopoietic chimerism achieved by a combined strategy of in utero hematopoietic stem cell transplantation and postnatal donor lymphocyte infusion
Blood,
July 18, 2002;
100(3):
804 - 812.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Eissner, G. Multhoff, A. Gerbitz, S. Kirchner, S. Bauer, S. Haffner, D. Sondermann, R. Andreesen, and E. Holler
Fludarabine induces apoptosis, activation, and allogenicity in human endothelial and epithelial cells: protective effect of defibrotide
Blood,
June 17, 2002;
100(1):
334 - 340.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Chen, X. Cui, C. Liu, and N. J. Chao
Prevention of graft-versus-host disease while preserving graft-versus-leukemia effect after selective depletion of host-reactive T cells by photodynamic cell purging process
Blood,
May 1, 2002;
99(9):
3083 - 3088.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Saito, Y. Kanda, M. Kami, K. Kato, N. Shoji, S. Kanai, T. Ohnishi, Y. Kawano, K. Nakai, T. Ogasawara, et al.
Therapeutic Potential of a Reduced-Intensity Preparative Regimen for Allogeneic Transplantation with Cladribine, Busulfan, and Antithymocyte Globulin against Advanced/Refractory Acute Leukemia/Lymphoma
Clin. Cancer Res.,
April 1, 2002;
8(4):
1014 - 1020.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Teshima, C. Liu, K. P. Lowler, G. Dranoff, and J. L. M. Ferrara
Donor Leukocyte Infusion from Immunized Donors Increases Tumor Vaccine Efficacy after Allogeneic Bone Marrow Transplantation
Cancer Res.,
February 1, 2002;
62(3):
796 - 800.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. F. Khouri, R. M. Saliba, S. A. Giralt, M.-S. Lee, G.-J. Okoroji, F. B. Hagemeister, M. Korbling, A. Younes, C. Ippoliti, J. L. Gajewski, et al.
Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality
Blood,
December 15, 2001;
98(13):
3595 - 3599.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Luznik, S. Jalla, L. W. Engstrom, R. Iannone, and E. J. Fuchs
Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide
Blood,
December 1, 2001;
98(12):
3456 - 3464.
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