The role of cytokines in acute graft-versus-host disease

Geoffrey R. Hill, Werner Krenger, James L.M. Ferrara

Research output: Contribution to journalReview articlepeer-review

61 Scopus citations

Abstract

Graft-versus-host disease (GVHD) remains the principal complication limiting the wider application of allogeneic bone marrow transplantation (BMT). Advances in basic immunology during the last decade have demonstrated how interactions between immunologically competent cells are governed by cytokines, and much recent research has focused on the roles of these mediators in the pathogenesis of acute GVHD. This article reviews current evidence that dysregulated cytokine production can be considered a cascade of sequential monocyte and T-cell activation that is responsible for many of the manifestations of acute GVHD. We suggest that cytokine dysregulation can be conceptualized in three phases. Phase 1 is initiated by the conditioning of the host, which induces inflammatory processes in recipient tissues. Donor T-cell activation by host alloantigens and subsequent cytokine secretion in phase 2 is facilitated by the consequences of phase 1. The T cell-derived cytokines of phase 2 activate distal inflammatory mediators, which, in synergy with T- and NK-cell mediated cytotoxicity, produce the systemic morbidity of GVHD-associated immunosuppression in phase 3. Data from both experimental and clinical studies involving cytokines and their blockade in the prevention or treatment of GVHD are reviewed.

Original languageEnglish
Pages (from-to)257-265
Number of pages9
JournalCytokines, Cellular and Molecular Therapy
Volume3
Issue number4
StatePublished - Dec 1997
Externally publishedYes

Keywords

  • Bone marrow transplantation
  • Cytokines
  • Graft-versus-host disease
  • IFN-γ
  • IL-1β
  • IL-2
  • LPS
  • TNF-α

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