Effect of CD25 monoclonal antibody on the rejection of heart allograft and the expression of cytokines

Objective To investigate the role of anti- interleukin-2 receptor (CD25) monoclonal antibody in the regulation of cytokine mRNA expression of IL-1β,IL-2,CD25,IL-4,IL-5,IL-6,IL-10,tumour necrosis factor (TNF)-α,interferon (IFN)-γ,in cardiac allografts to elucidate its immunological mechanism and the role in rats' cardiac transplantation.Methods These in vivo studies were conducted using a rat MHC mismatch SD to Wistar heterotopic cardiac transplant model.Simulect,an anti-CD25 antibody was used to treat the allograft rejection.The survival of allografts was observed.The rat hearts in each group were harvested on day 1,3,5,7,9,11,14 post-transplantation.Cytokine mRNA expression was detected by semiquantitative RT-PCR.Results In control group,rejection of the cardiac allografts occurred at (8.3±1.7) days after transplantation.The rats who received CsA rejected the cardiac allograft at (26.4±5.7) days post-transplant.The survival of the ras treated with Simulect was increased to (29.2±7.1) days (P0.05 vs controls).The longest survivial of (55.0±16.0) days was obtained by combined use of Simulect with CsA (P0.001 vs controls).In heart tissue,the CD25 mRNA expression was undetectable or very weak.However,in rejecting allografts from untreated recipients,the CD25 expression was remarkably increased,while anti-CD25 decreased the CD25 expression in heart graft.Furthermore,in untreated allografts IL-2,TNFα and IFN-γ were strongly expressed,but markedly decreased after simulect treatment.Finally,IL-4,IL-5,IL-6 and IL-10 expression was strong in the anti-CD25-treated allografts.Conclusion Anti-CD25 antibody treatment may not only neutralize CD25 activity but also play a role in altering cytokine mRNA expression and prolong the survival of allografts.