Inhibition of interleukin-1 by an interleukin-1 receptor antagonist prevents graft-versus-host disease

Graft-versus-host disease (GVHD) is the major complication of allogeneic bone marrow transplantation (BMT). Dysregulation of inflammatory monokines such as tumor necrosis factor α (TNFα) 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-1α as well as the gene for TNFα 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.