INHIBITION OF ACUTE GRAFT
VERSUS HOST DISEASE (aGVHD) BY THE ALKALOID SINOMENINE IN THE MOUSE MODEL
Wu Jianchun1, Zhu Weiguo1,
Yao Yingmin1, Wang Quanxing2, Zhang Minghui2, Cao Xuetao2
1.Department of Pediatrics,
Nanfang Hospital, Guangzhou 510515, China
2.Department of Immunology,
Second Military Medical University, Shanghai 200433, China
Objective: To characterize the effectiveness and the immunological
mechanism of purified alkaloid sinomenine (SN),an extracts of the plant
Sinomenium Acutum used in Traditional Chinese Medicine for rheumatic
diseases , suppressing the development of acute GVHD in a MHC-mismatched
murine model
Methods: Different doses of the purified SN alone or in combination with
subtherapeutic dose of Cyclosporin A (CsA) was administered into mice with
aGVHD (C57BL6BALB/C irradiated BMT model), the mean survival time (MST) was
compared , histology study and further in vitro experiments was made.
Results: Administrations of subtherapeuticSN (25mg/kg) or CsA (5 mg/kg)
alone could not prolong the MST (15.90 days for SN and 16.00 days for
CsA,P>0.05).By contrast, combined therapy with SN and CsA in the same
dose alone demonstrated a synergistic effect, resulting in significant
prolongation of MST(44.40 days, P<0.01),showing the same effects of
therapeutic dose of CsA (20 mg/kg) treatment (MST41.00 days).Histology
study of liver, gut and skin from the recipients on day 14 after BMT showed
that the morphologic damages of the tissues induced by GVHD lightened in
the treatment groups which have long MST. In vitro studies demonstrate that
SN inhibit the proliferation and function of bone marrow derived dendritic
cells (DCs) and T lymphocytes.
Conclusion: SN synergistically enhanced the anti-GVHD effects of
established immunosuppressive drug CsA, indicating that SN is a novel
immunosuppressive agent affecting DCs and T cell function .The potential
role of SN in transplantation should be investigated in more details.