The primacy of the gastrointestinal tract as a target organ of acute graft-versus-host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation

Acute graft-versus-host disease (GVHD), the major complication of allogenei c bone marrow transplantation (BMT), limits the application of this curativ e but toxic therapy. Studies of inflammatory pathways involved in GVHD in a nimals have shown that the gastrointestinal (GI) tract plays a major role i n the amplification of systemic disease. Damage to the GI tract increases t he translocation of inflammatory stimuli such as endotoxin, which promotes further inflammation and additional GI tract damage. The GI tract is theref ore critical to the propagation of the "cytokine storm" characteristic of a cute GVHD, Experimental approaches to the prevention of GVHD include reduci ng the damage to the GI tract by fortification of the GI mucosal barrier th rough novel "cytokine shields" such as IL-11 or keratinocyte growth factor. Such strategies have reduced GVHD while preserving a graft-versus-leukemia effect in animal models, and they now deserve formal tasting in carefully designed clinical trials,(Blood, 2000; 95:2754-2759) (C) 2000 by The Americ an Society of Hematology.