Transplant Immunology 1997; 5: 315-319 Inhibition of murine chronic graft-versus- host disease by the chloroform extract of zyxwvutsrq Tripterygium wilfordii Hook f Kazuhito Asanoa, Ying Yub, Takako Kasaharab and Tadashi Hisamitsub zyxwvutsrq ‘Deparfment of Medical Biology and bDepatiment of Physiology School of Medicine, Show a University ,Shinagaw a- ku, To@ 0 Received 23 June 1997; accepted for publication 21 August 1997 Abstractr The effects of chloroform extract of lhpteygium FW’oti zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONM Hookf (TWH extract) on chronic graft- versus-host disease (GVHD) were examined in a murine experimental model. Chronic GVHD was induced by intravenous transfer of parental DBA/2 spleen cells into unirradiated (C57BU6 x DBAL?)Fl recipient mice. The effects of TWH extract on GVHD were assessed by measuring both the degree of splenomegaly and the total serum IgE levels 3 weeks after the cell transfer. Subcutaneous administration of ‘IWH extract once a day for 3 weeks suppressed chronic GVHD in a dosedependent manner. Significant suppression of splenomegaly was Srst noted in mice treated with 7.5 p.&kg of the agent. The maximum inhibition was observed when mice were treated with more than 10.0 &~/kg(but not 5.0 ug/kg) caused complete suppres- sion of serum IgE hyperproduction. The ability of donor T cells purified from recipient spleen cells to produce interleukin 4 in response to stimulation with anti-CD3 monoclonal antibody was signhicantly abrogated when recipient mice were treated with 10.0 clg/kgof the agent. These results strongly suggest that TWH extract will be an addition to the cohort of immunosuppressive therapies used in solid organ and bone marrow transplantation. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Introduction Although allogeneic bone marrow transplantation is the current treatment for a wide variety of haematologic, metabolic and oncologic disorders, graft-versus-host disease (GVHD) remains a major complication and risk factor.lY2GVHD can be subdivided into acute and chronic forms, which are generally believed to be a systemic manifestation of alloactivation of donor T cells to recipient alloantigens.3P Accordingly, attempts to modulate GVHD have included both rigorous immune sup- pression in the host through a variety of immunosuppressants2 and pretreatment of donor inoculum to remove T cells5 Recently, administration of immunosuppressive agents, such as FK-506, cyclosporin A and rapamycin,6,7 and monoclonal antibodies against T cell surface antigenszsP9 were shown to significantly reduce the degree of GVHD in experimental and clinical therapy, indicating that these immunosuppressive strategies will be useful in the prevention and treatment of GVHD in humans. Tripteggium wilfordii Hook f (TWH), a traditional Chinese Address for correspondence: K Asano, Department of Medical Biology, School of Medicine, Showa University, 1-5-g Hatanodai, Shinagawa-ku, Tokyo 142, Japan. 0 Arnold 1997 herb, has been used successfully in the treatment of auto- immune diseases such as rheumatoid arthritis, system lupus erythematosus and psoriasis.‘oP11 There is much evidence that many fractions extracted from TWH showed inhibitory actions on both lym 4 hocyte proliferation induced b stimulation in vitro’ l3 and skin allograft rejection.’ !Y mitogenic ‘Iliptolide, one of the most active components in TWH extract, was also reported to suppress the mixed lymphocyte reaction and cytotoxic T cell activity. l3 However, as far as we know, further investigation of the effects of these extracts on immune res- ponses, especially GVHD, has not yet been reported. In murine models, it is possible to reproducibly generate either an acute or chronic GVHD. One of the most widely used models is the GVHD occurring when parental lymphocytes are transferred to unit-radiated Fl hybrid recipients. In the case of (C57BU6 x DBA/2)Fl hybrid mice, transfer of parental C57BU6 spleen cells results in an acute GVHD, whereas transfer of parental DBA/2 spleen cells results in a chronic GVHD.14P15 In this study, we have investigated the effects of TWH extract on GVHD using a murine experimental model, and the data obtained indicate that TWH extract prevents chronic GVHD by inhibition of T cell activation in response to an allogeneic stimulus. 0966-3274(97)TI197OA