Keratinocyte Growth Factor (KGF) ameliorates GVHD following allogeneic murine BMT

KGF is important in tissue repair and wound healing and its administration can abrogate chemically-induced tissue damage in rodents. We investigated its use as a therapeutic agent for the prevention or treatment of GVHD-induced tissue damage, morbidity and mortality in our established murine allogeneic BMT model. B10.BR (H2^k) recipient mice (n=8/group) were lethally irradiated and transplanted with C57BL/6 (H2^b) BM with spleen cells (BMS) as a source of GVHD-causing T cells. KGF-treated mice (5mg/kg/day sq days -6,-5,-4 pre-BMT) receiving BMS exhibited better survival than those not receiving KGF (p=0.02). Cyclophosphamide (Cy), a common component of TBI-containing regimens, was given to other cohorts of mice at a dose of 120mg/kg/day ip on days -3,-2 prior to BMT. KGF-treated mice had a better survival rate than those not given KGF (p=0.003). KGF-treated recipients given TBI or Cy/TBI BMS were, however, not GVHD-free as shown by lower body weights compared to BM groups. GVHD target tissues were assessed histologically using standard GVHD criteria during a 48 day post-BMT observation period. KGF ameliorated GVHD-induced tissue damage in the liver, spleen and lung (almost completely in some recipients) and moderately so in the colon, even with Cy conditioning. These studies demonstrate that KGF has potential as an anti-GVHD therapeutic agent.