Objective   To evaluate the effect of anti-RANTES monoclonal antibody in combination with ciclosporin (CsA) upon inhibiting the rejection response during secondary heart transplantation in mouse models.

  Methods   BALB/c mouse models were used as the donors and C57BL/6 mice were utilized to establish secondary heart transplantation recipient models. The animals were randomly divided into the control (physiological saline, n=6), A (anti-RANTES monoclonal antibody treatment, n=6), B (CsA treatment, n=6) and C groups (anti-RANTES monoclonal antibody combined with CsA treatment, n=6). The survival time of heart after secondary transplantation was observed. The degree of acute heart rejection was assessed by histopathological analysis. The relative expression levels of RANTES, interleukin(IL)-2, IL-10, interferon(IFN)-γ and transcription growth factor(TGF)-β messenger ribonucleic acid (mRNA) in the heart grafts were quantitatively measured by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). The serum levels of RANTES, IFN-γ, IL-2, IL-10 and TGF-β were detected by enzyme-linked immune absorbent assay (ELISA).

  Results   The heart grafts of all mice survived after secondary cardiac transplantation. Compared with the controlgroup, the survival time of hearts in group A, B and C was significantly prolonged (all P＜0.01). Pathological staining revealed that the quantity of infiltrated inflammatory cells in group C was significantly decreased than those in the other groups. The expression levels of heart RANTES, IFN-γ and IL-2 mRNA in group C were significantly down-regulated, whereas the expression levels of IL-10 and TGF-β mRNA were considerably up-regulated compared with those in the other three groups (all P＜0.05). The serum levels of RANTES, IL-2 and IFN-γ in group C were significantly down-regulated, whereas the serum contents of IL-10 and TGF-β were considerably up-regulated compared with those in the other three groups (all P＜0.05).

  Conclusions   Combined application of anti-RANTES monoclonal antibody and CsA can effectively induce the immune tolerance to secondary cardiac transplantation and prolong the survival time of the cardiac grafts in mouse models.