Cytokines, viruses, and graft-versus-host disease

Proinflammatory cytokines released by host tissues during conditioning treatment and interferon gamma released from donor T cells play a major role in acute graft-versus-host disease (GVHD). In the past year the interaction of cytokines has been elucidated further. Host antigen-presenting cells play a key role in the induction of allogeneic recognition. Their activity is modulated by cytokines such as flt3-ligand, viruses, and donor T cells. Expansion of donor T cells is crucial for the pathogenesis of acute GVHD. Cytokines of the T helper 1 response-IFN-gamma, IL-12, and IL-18-regulate the expansion of donor and host cells via the induction of Fas and FasL and subsequent apoptosis. However TNF-alpha, FasL, and IL-1 also cause damage to target cells. Cytokine and receptor gene polymorphism has an impact on the activity of both host and donor cell activation. Genetic factors, conditioning treatment, lipopolysaccharides (LPS) from gram-negative microorganisms, viral infections, and donor T cells determine the activity level of host antigen-presenting cells and macrophages, which have an impact on acute GVHD and other complications of allogeneic stem cell transplantation.