RESUMO
The aim of our study was to evaluate the efficacy of FK506, mycophenolate mofetil (MM) and aminoguanidine (AMG) on infiltration of macrophages (MPHs), neutrophils (NPHs) and dendritic cells (DC) into corneal grafts during the early phases after transplantation (Tx). Tx was performed in mice (C57BL/10 to BALB/c). Therapy included FK506 (0.2 mg/kg), MM (30 mg/kg) or AMG (0.1 g/kg), started at the day of Tx and was injected i.p. daily. Corneas were excised on the third and seventh day after Tx. Immunohistological evaluation using antibodies against MPHs, NPHs and DC was performed and corneal grafts were assessed in the periphery and in central part of the cornea separately. On the third day after Tx, a massive infiltration of MPHs and NPHs into corneal grafts was revealed; the DC infiltration was lower in all treated groups. Treatment with FK506 and MM led to a significant reduction of NPHs in the centers of the grafts, but not of MPHs. In contrast, AMG significantly reduced MPHs migration into allografts on the third day after Tx, whereas NPHs infiltration has not been attenuated. However, immunosuppressants had no influence on the infiltration of DC during early phases after Tx.
Assuntos
Córnea/efeitos dos fármacos , Transplante de Córnea , Rejeição de Enxerto/prevenção & controle , Guanidinas/farmacologia , Imunossupressores/farmacologia , Ácido Micofenólico/análogos & derivados , Tacrolimo/farmacologia , Animais , Contagem de Células , Córnea/imunologia , Córnea/cirurgia , Células Dendríticas/efeitos dos fármacos , Feminino , Rejeição de Enxerto/imunologia , Guanidinas/uso terapêutico , Imunossupressores/uso terapêutico , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Modelos Animais , Ácido Micofenólico/farmacologia , Ácido Micofenólico/uso terapêutico , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Tacrolimo/uso terapêutico , Fatores de TempoRESUMO
The purpose of our study was to compare the effectiveness of immunosuppressive drugs on the prevention of allograft rejection in a murine model of low-risk and high-risk keratoplasty. The therapy included FK 506 (tacrolimus; 0.2 mg/kg), mycophenolate mofetil (30 mg/kg), aminoguanidine (0.1 g/kg), and combination of FK506 + mycophenolate mofetil or FK506 + aminoguanidine. The results obtained from the Gray's survival model stratified according to the type of subjects suggest that a major rejection risk reduction was achieved using FK506; good results also were obtained for mycophenolate mofetil. Although the point estimates of both the survival and relative risk of rejection suggest a deferred effect of the combination FK506 + mycophenolate mofetil, this finding did not prove statistically significant.
