Role of Interferon-gamma in GVHD and GVL.

Interferon (IFN)-gamma, a potent proinflammatory cytokine produced by multiple types of cells (e.g., activated T, NK and NKT cells), plays important and complex roles in both innate and adaptive immune responses. There may be a correlation between the IFNgamma level and GVHD severity in patients receiving allogeneic hematopoietic cell transplantation. However, such a correlation may just reflect the presence of large numbers of activated T cells, and does not necessarily imply a harmful role of IFN-gamma in the pathogenesis of GVHD. There has been increasing experimental evidence that IFN-gamma is not required and may even inhibit GVHD. Paradoxically, IFN-gamma facilitates graft-versus-leukemic (GVL) effects. Thus, IFN-gamma blockade is likely deleterious in patients after allogeneic hematopoietic cell transplantation, and not beneficial as previously suggested.