Immune restoration of local xenogeneic graft-versus-host reaction in cancer patients in vitro and reversal of cyclophosphamide-induced immune suppression in the rat in vivo by fractionated Astragalus membranaceus


Chu DT, Sun Y, Lin JR




Chung Hsi I Chieh Ho Tsa Chih


Through the process of fractionation, purification by gel filtration chromatography and thereafter the screening with an in vitro local xenogeneic graft-versus-host reaction (XGVHR) model, a fraction was identified as a potent immunorestorative agent and was designated "Fraction 3" (F3). Using the XGVHR in vitro as a model assay for T cell function again, F3 was studied on mononuclear cells (MNC) from 13 cancer patients and exhibited significant immunorestorative activity, with an increase in local XGVHR (compared to untreated cells) of 151.34 +/- 46.02 mm3 vs 57.80 +/- 16.44 mm3, P less than 0.001. The in vitro augmented immune reactions induced by F3 in cancer patients also significantly exceeded the local XGVHR observed in the untreated MNC derived from 9 normal donor controls (94.15 +/- 9.16 mm3, P less than 0.005). In a newly developed in vivo XGVHR animal model, pretreatment of rats with F3 resulted in a significant abrogation of the local XGVHR with a reversal of the immunosuppressive effect of cyclophosphamide from 99.42 +/- 9.2 mm3 (positive control) to 39.78 +/- 8.3 mm3 (P less than 0.001). This reversal was complete as the volume of the abrogated local XGVHR was comparable to that of the negative control (no cyclophosphamide- priming, saline injection only) 34.79 +/- 5.69 mm3 (P greater than 0.1). These results suggest that F3 retained the immunopotentiating activity of the original crude extract and form the rational basis for the use of Astragalus in immunotherapy.