Objective: To evaluate the effects of Tripterygium hypoglaucum (level) Hutch (THH) on cytokine production in acute graft-versus-host disease (aGVHD)mice and explore the mechanisms.
Methods: 2 x 10(7) bone marrow cells mixed with 2 x 10(7) spleen cells from the same C57BL/6 mouse were transplanted into the myeloablative irradiated inbred BALB/c mouse to establish a aGVHD model. The experiments were designed as follows: control group (group A), CsA prophylaxis group (group B), THH prophylaxis group (group C), and combined THH with CsA prophylaxis group (group D). aGVHD was assessed by histologic changes of skin, liver and intestines. Chimerism was detected by H-2b molecular expression on recipient mice bone marrow cells with flow cytometer. Serum concentrations of IFN-gamma, IL-4 and IL-10 were determined by ELISA.
Results: The serum concentrations of IFN-gamma in group B, C, D were significantly lower than that in group A, while those of IL-10 was significantly higher than that in group A (P < 0.05). There was no changes in concentration of IL-4 in all the groups (P > 0.05). The median survival time for group A was nine days, while that of group B, C, D each was more than 30 days being significantly longer than that of group A (P < 0.05). The recipient mice of group A displayed significant clinical symptoms of GVHD, and died within 20 days; whereas those of group B, C, D showed only ruffled fur and uplift posture. Histologic changes of liver and intestines in group B and C displayed a few lymphocytes infiltration while the histologic morphology of skin, liver and intestines in the survived mice of group D was normal. Allogeneic chimerism rates of group B, C, D at day 30 after allo-BMT were (99.18 +/- 0.58)%, (97.68 +/- 0.59)%, and (99.15 +/- 0.11)%, respectively.
Conclusion: THH could regulate the production of cytokines and prevent aGVHD. THH and CsA at low dose combination showed synergic effect in preventing aGVHD.