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

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

Immunomodulatory effect of cimetidine on the proliferative responses of splenocytes from T. cruzi-infected rats

O efeito imunomodulatorio da Cimetidine (CIM), um antagonista do receptor de histamina-tipo 2, foi avaliado na resposta blastogenica a Con A em celulas de ratos Wistar Furth (WF) infectados pela cepa Y de Trypanosoma cruzi (T.cruzi). Foi observado que apenas na concentracao de "10 POT. -3"M de Cimetidine houve amplificacao da resposta blastogenica de esplenocitos normais a Con A. Entretanto, a capacidade mitogenica de esplenocitos de animais infectados foi restaurada na presenca de molaridades da droga que variaram entre "10 POT. -8" a "10 POT. -3". Os resultados demonstraram que a CIM tem o potencial de modular a resposta mitogenica de celulas de animais infectados pelo T.cruzi, sugerindo um papel imunoregulatorio da histamina e/ou celulas que expressam receptores H2 nesta infeccao.