Inhibitory effects of cimetidine on graft survival of allotransplanted rats submitted to an active-passive enhancement protocol

ABSTRACT

The objetive of the presented study was to determine wheter cimetidine, a type-2 histamine receptor antagonist, inhibits the immunological enhancement of allografted rats achieved by treatment with donor antigen plus anti-donor antibody. Groups of rats submitted to this active-passive enhancement protocol and treated ip with 30 (APEC30; Group I; N = 4) or 60 (APEC 60; Group II; N = 8) mg/day cimetidine for 14 days had a significantly shorter graft survival (20.2 ñ 5.1 and 11.1 ñ 2.6 days, respectively) than the control group (animals submitted to the enhancement protocol and killed on day 72 after transplant when the graft was beating normally; APE; Group III; N = 6; P<0.05). On the other hand, these animals had a significantly longer graft survival than rats allotransplanted but not treated for enhancement (ALLO; Group V; N = 5; 8.2 ñ 0.8 days). The surgical control, consisting of isotransplanted animals, had a long-term survival (ISO; Group V; N = 6; rats killed 120 days after transplant with the graft beating normally). Animals treated with cimetidine, but not submitted to the enhancement protocol (AC 60; Group IV, N = 4) had a significantly shorter graft survival (6.25 ñ 0.5) than the allotransplanted animals (Group V). These results indicate inhibition of the suppressor mechanisms which participate in this type of immunological enhancement