Recent clinical observation reported that there was a significant correlation between change in circulating vascular endothelial growth factor (VEGF) levels and the occurrence of severe acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the action mechanisms of VEGF in GVHD have not been demonstrated.
This study investigated whether or not blockade of VEGF has an effect on acute GVHD in a lethally irradiated murine allo-HSCT model of B6 (H-2 b)→B6D2F1 (H-2 b/d). Syngeneic or allogeneic recipient mice were injected subcutaneously with anti-VEGF peptides, dRK6 (50 µg/dose) or control diluent every other day for 2 weeks (total 7 doses).
Administration of the dRK6 peptide after allo-HSCT significantly reduced survival with greaterclinical GVHD scores and body weight loss. Allogeneic recipients injected with the dRK6 peptide exhibited significantly increased circulating levels of VEGF and expansion of donor CD3 + T cells on day +7 compared to control treated animals. The donor CD4 + and CD8 + T-cell subsets have differential expansion caused by the dRK6 injection. The circulating VEGF levels were reduced on day +14 regardless of blockade of VEGF.