International Journal of Hematology

DOI: 10.1007/s12185-011-0803-1 Pages: 571-577

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

1. University of Michigan Blood and Marrow Transplantation Program

Correspondence to:
John E. Levine
Tel: +1-734-9368456
Fax: +1-734-9368788
Email: jelevine@med.umich.edu

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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.

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