Prevention of acute GVHD in mice by treatment with Tripterygium hypoglaucum Hutch combined with cyclosporin A.

OBJECTIVE: To elucidate the protective roles and the underlying mechanism of Tripterygium hypoglaucum Hutch (THH) in mice graft-versus-host disease (GVHD).
METHODS: BALB/c (H-2k(d)) mice were firstly treated with total body irradiation and infused with a mixture of bone marrow and spleen cells from C57BL/6. Then the severity of acute GVHD (aGVHD), chimeras of donor cells, inflammatory cytokines (IFN-γ, IL-4, and IL-10) of plasma, and regulatory T cells were evaluated to elucidate the different drug combinations and concentrations of cyclosporin A (CsA) and THH in preventing aGVHD.
RESULTS: The control group treated with phosphate buffer solution displayed more obvious ruffled hair, hunched posture, diarrhea, reduced weight and more lymphocytes infiltration into the spleen and intestine than these treated with CsA, THH or low-dosed CsA combined with THH, especially those treated with low-dosed CsA combined with THH. No significant differences were observed in the chimeras of donor cells and survival rate among the CsA, THH, or CsA combined with THH-treated groups. Further studies implied that THH might reduce the aGVHD by increasing IL-10, decreasing IL-4, activating Treg cell, and maintaining a relatively high Foxp3 mRNA level.
CONCLUSION: THH decreased the occurrence of mouse aGVHD and prolonged the survival time by increasing the levels of CD(4)(+)/CD(25)(+) T cells, regulating the cytokine secretion and promoting the expression of Foxp3.