The absence of donor-derived IL-13 exacerbates the severity of acute graft-versus-host disease following allogeneic bone marrow transplantation

Abstract

Acute graft versus host disease (aGVHD) after allogeneic bone marrow transplantation (allo-BMT) predominantly involves a Th1-type cytokine response. Interestingly, the Th2-cytokine, Interleukin-13 (IL-13), produced by alloreactive donor T cells in vitro was recently shown to correlate with clinical aGVHD severity. Using an established mouse model, we show that the systemic cytokine milieu following allo-BMT with IL-13−/− donors is characterized by decreases in serum Th2 cytokines and an increase in serum TNFΑ, and ultimately correlates with higher aGVHD mortality compared to allogeneic controls. In vitro studies further demonstrate that both exogenous and T cell-derived IL-13 can regulate TNFΑ production by macrophages following lipopolysaccharide stimulation. Thus, donor-derived IL-13 may have a role in modulating inflammatory cytokine release that is associated with aGVHD. Pediatr Blood Cancer 2008;50:911–914. © 2007 Wiley-Liss, Inc.