CYTOKINE DYSREGULATION AS A MECHANISM OF GRAFT-VERSUS-HOST DISEASE

Craft versus host disease (GVHD) remains the major complication of allogeneic bone marrow transplantation. T cells in the donor bone marrow recognize and react against host alloantigens and thereby initiate GVHD, but the precise mechanisms by which host tissues are damaged remain unclear. Recently, several convergent lines of evidence have suggested that inflammatory cytokines act as mediators of acute GVHD. Most of the clinical manifestations of GVHD may in fact be due to the dysregulated production of cytokines by T cells and other inflammatory cells. The complex interactions among cytokines and their cellular targets suggest that individual cytokines may play an important and distinctive role in the pathophysiology of GVHD. Perturbation of the cytokine network may function as a final common pathway of target organ damage, and the rapid onset of severe, acute GVHD can be considered a 'cytokine storm.'