International Journal of Hematology

, Volume 78, Issue 3, pp 181–187 | Cite as

The Pathophysiology of Acute Graft-versus-Host Disease

  • James L. M. Ferrara
  • Kenneth R. Cooke
  • Takanori Teshima
Progress in Hematology

Abstract

The pathophysiology of acute graft-versus-host disease (GVHD) is a complex process that can be conceptualized in three phases. In the first phase, high-dose chemoradiotherapy causes damage to host tissues, including a self-limited burst of inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin 1. These cytokines activate host antigen-presenting cells (APCs). In the second phase, donor T-cells recognize alloantigens on host APCs. These activated T-cells then proliferate, differentiate into effector cells, and secrete cytokines, particularly interferon (IFN)-γ. In the third phase, target cells undergo apoptosis mediated by cellular effectors (eg, donor cytotoxic T-lymphocytes) and inflammatory cytokines such as TNF-α. TNF-α secretion is amplified by stimuli such as endotoxin that leaks across damaged gastrointestinal mucosa injured by the chemoradiotherapy in the first phase. TNF-α and IFN-γ cause further injury to gastrointestinal epithelium, causing more endo-toxin leakage and establishing a positive inflammatory feedback loop. These events are examined in detail in the following review.Int J Hematol. 2003;78:181-187. 2003 The Japanese Society of Hematology

Key words

Bone marrow transplantation Graft-versus-host disease Cytokines TNF-α IL-1β 

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Copyright information

© The Japanese Society of Hematology 2003

Authors and Affiliations

  • James L. M. Ferrara
    • 1
  • Kenneth R. Cooke
    • 1
  • Takanori Teshima
    • 1
  1. 1.University of Michigan Cancer Center, Bone Marrow Transplant ProgramAnn ArborUSA

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