Hematotoxicity of the Chinese herbal medicine Tripterygium wilfordii Hook f in CD34-positive human bone marrow cells

T2, a chloroform/methanol extract of the herb Tripterygium wilfordii Hook f , has been used in China for the treatment of autoimmune and inflammatory d iseases for many years. Recent experimental evidence has confirmed that T2 has potent antiinflammatory and immunosuppressive activity, and a United St ates Food and Drug Administration-approved clinical trial is currently expl oring the efficacy of T2 in the treatment of rheumatoid arthritis. Despite the potential therapeutic benefits of T2, there is ample documentation that T2 is toxic, targeting, among other things, the hematopoietic system, and its use has resulted in cases of leukopenia, thrombocytopenia, and aplastic anemia. This investigation was undertaken to characterize the in vitro eff ects of T2 on primary human CD34-positive (CD34+) bone marrow cells. Our re sults demonstrate that T2 has a potent inhibitory effect on the clonogenic response of human bone marrow cells to exogenously added hematopoietic grow th factors. The inhibition of colony formation by T2 is not the result of d irect cytotoxicity or increased apoptosis and indicates a functional suppre ssion of hematopoiesis. Additional experiments demonstrate that T2 also alt ers transcriptional regulation in bone marrow cells by inhibiting nuclear f actor-kappa B. This transcription factor is found in CD34+ bone marrow cell s and has been recently shown to be a requirement for colony formation. The se results demonstrate that therapeutic concentrations of T2 exert a signif icant hematotoxic effect by inhibiting growth factor response in CD34+ bone marrow cells and suggest that inhibition of nuclear factor-kappa B may pla y a role in the blood dyscrasias encountered with the use of this drug.