Blood, Vol. 95 No. 2 (January 15), 2000:
pp. 705-710
PG27, an extract of Tripterygium wilfordii hook
f, induces antigen-specific tolerance in bone marrow
transplantation in mice
Yanfei Chen,
Defu Zeng,
Paul G. Schlegel,
John Fidler, and
Nelson J. Chao
From the Divisions of Hematology/Oncology and Immunology and
Rheumatology, Stanford University, Stanford, CA; and Pharmagenesis
Inc., Palo Alto, CA.
PG27, an active fraction purified from an extract of a Chinese herb,
Tripterygium wilfordii hook f, was used to prevent
graft-versus-host disease (GVHD) in a murine model. Lethally irradiated
BALB/c (H-2d) recipients of B10.D2 (H-2d) donor
grafts were given daily intraperitoneal injections of PG27 (40 mg/kg
per day) for the first 35 days after transplantation. Control mice were
given daily injections of solvent vehicle (Ethanol and Cremophor EL).
All the control recipients (15/15) died of GVHD within 90 days, but all
the recipients given prophylactic treatment with PG27 (15/15)
survived beyond 100 days without any signs of GVHD. Furthermore, the
GVHD-free recipients were used as donors, and their bone marrow and
spleen cells were transplanted into lethally irradiated normal BALB/c
(same party) or lethally irradiated normal C3H (H-2k, third
party) mice. Although 10 of 10 same-party recipients survived more than
100 days without any signs of GVHD, 10 of 10 third-party C3H recipients
died of GVHD within 40 days. Further studies of PG27 in the murine
BCL1 leukemia/lymphoma model demonstrated that animals treated with PG27 partially retained the graft-versus-leukemia (GVL) effect of the graft without GVHD. These results suggest that
treatment with PG27 induces host-specific tolerance and retains the GVL
effect of allogeneic marrow grafts.
