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Inhibition of interleukin-1 by an interleukin-1 receptor antagonist
prevents graft-versus-host disease
PL McCarthy , S Abhyankar, S Neben, G Newman, C Sieff, RC Thompson, SJ Burakoff and JL Ferrara
Division of Hematology, Brigham and Women's Hospital, Boston, MA.
Graft-versus-host disease (GVHD) is the major complication of allogeneic
bone marrow transplantation (BMT). Dysregulation of inflammatory monokines
such as tumor necrosis factor alpha (TNF alpha) has been noted in both
clinical and experimental GVHD. We present evidence that interleukin-1
(IL-1), another inflammatory monokine, is an important mediator of GVHD.
Expression of the gene for IL-1 alpha as well as the gene for TNF alpha is
increased in the skin of mice with GVHD. Inhibition of IL-1 function by the
in vivo administration of IL-1 receptor antagonist (IL-1ra) reduces the
immunosuppression and mortality of GVHD without impairing the engraftment
of hematopoietic stem cells. GVHD thus appears to be a systemic
inflammatory process in which monokines, especially IL-1, appear to be
important mediators. Inhibition of IL-1 by IL-1ra represents a novel
approach to the understanding and control of GVHD.
Volume 78,
Issue 8,
pp. 1915-1918,
10/15/1991
Copyright © 1991 by The American Society of Hematology
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