Background.

PG490–88 is a water soluble, semisynthetic derivative of a novel compound PG490 (triptolide) purified from the Chinese herb Tripterygium Wilfordii Hook F.

Methods.

PG490–88 was administrated into recipient mice in a model (B10. D2→ BALB/c) of lethal graft-versus-host disease (GVHD) to study the effects of PG490–88 on GVHD and on the various steps involved in the pathological course of GVHD.

Results.

Injection of PG490–88 ip at a dose of 0.535 mg/kg/day for the first 3 weeks after transplantation protected all the recipients from developing GVHD up to 100 days after transplantation. PG490–88 inhibited in vivo both CD4+ Vβ3+ and CD8+ Vβ3+ T cell (alloreactive T cells in this model) expansion in the spleen by 64.09 and 34.02%, respectively, at the time when Vβ3+ cell expansion was in the logarithmic phase (day 3 after transplantation). Intracellular cytokine staining without further in vitro activation demonstrated 47.42% inhibition of IL-2 production among CD4+ spleen cells in PG490–88-treated mice as compared to GVHD control on day 3 after transplantation. In contrast, CD25 (α chain of interleukin-2 receptor) expression did not differ.

Conclusions.

PG490–88 is highly effective in prevention of murine GVHD. The immunosuppressive effect of PG490–88 is mediated by inhibition of alloreactive T cell expansion through interleukin-2 production.