Alantolactone ameliorates graft versus host disease in mice
Özet
The anti-inflammatory and immunosuppressive drugs which are used in the treatment of Graft-versus-Host
Disease (GVHD) have limited effects in controlling the severity of the disease. In this study, we aimed to
investigate the prophylactic effect of Alantolactone (ALT) in a murine model of experimental GVHD.
The study included 4 BALB/c groups as hosts: Naïve (n = 7), Control GVHD (n = 16), ALT-GVHD (n = 16), and
Syngeneic transplantation (n = 10). Busulfan (20 mg/kg/day) for 4 days followed by cyclophosphamide (100
mg/kg/day) were administered for conditioning. Allogeneic transplantation was performed with cells collected
from mismatched female C57BL/6, and GVHD development was monitored by histological and flow cytometric
assays. Additionally, liver biopsies were taken from GVHD patient volunteers between ages 2–18 (n = 4) and
non-GVHD patients between ages 2–50 (n = 5) and cultured ex vivo with ALT, and the supernatants were used
for ELISA.
ALT significantly ameliorated histopathological scores of the GVHD and improved GVHD clinical scores.
CD8+ T cells were shown to be reduced after ALT treatment. More importantly, ALT treatment skewed T cells to a
more naïve phenotype (CD62L+ CD44− ). ALT did not alter Treg cell number or frequency. ALT treatment appears
to suppress myeloid cell lineage (CD11c+). Consistent with reduced myeloid lineage, liver and small intestine
levels of GM-CSF were reduced in ALT-treated mice. IL-6 gene expression was significantly reduced in the intestinal tissue. Ex vivo ALT-treated liver biopsy samples from GVHD patients showed a trend of decrease in proinflammatory cytokines but there was no statistical significance.
Collectively, the data indicated that ALT may have immunomodulatory actions in a preclinical murine GVHD
model.
