Abrogation of the local xenogeneic graft versus host reaction by preinjection of cimetidine to the immunosuppressed host rats: an experimental model for testing preclinical immunorestorative activity in vivo.
The local xenogeneic graft-vs-host reaction (XGVHR) is mediated by competent T lymphocytes. It was effectively used as a practical bioassay to assess the in vitro immunomodulatory effects of several drugs on cells derived from cancer patients. A modified version of the XGVHR model was recently developed primarily for preclinical evaluation of in vivo immunorestoration induced by experimental biological response modifiers (BRMs). A well-defined biological response modifier, cimetidine, was injected into Cytoxan-primed rats prior to their inoculation with xenogeneic human mononuclear cells. The cimetidine treatment induced a partial abrogation of the immunosuppressive effect of Cytoxan as manifested by a significant decline in the volume of the XGVHR from 115.23 +/- 15.72 mm3 (positive control) to 67.3 +/- 11.41 mm3 (P less than 0.01). This abrogation of Cytoxan-induced immunosuppression by cimetidine was incomplete since the XGVHR without Cytoxan (negative control, saline only) was still significantly lower (45.12 +/- 4.55 mm3; P less than 0.01). The effect of cimetidine injection in vivo appeared to be dose dependent and did not exhibit any nonspecific toxic effect to the mononuclear cell inoculum. These results indicate that the model can serve as a useful tool in the preclinical evaluation of newly developed immunorestorative biological response modifiers.
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology; D006087:Graft vs Host Reaction / Q000187:drug effects*; D007108:Immune Tolerance / Q000187:drug effects*; D008297:Male; D008954:Models, Biological; D051381:Rats; D011917:Rats, Inbred Lew; D014183:Transplantation, Heterologous
D002927:Cimetidine; D003520:Cyclophosphamide