Article ID Journal Published Year Pages File Type
3392143 Transplant Immunology 2012 6 Pages PDF
Abstract

This study aimed to evaluate the role of combined use of rapamycin and leflunomide(Lef) on the prevention of acute allograft rejection in rats. After cardiac transplantations, rats were randomly divided into untreated group, rapamycin group, Lef group and rapamycin + Lef group. The drugs were given by gavage from day 0 to day 9 after transplantations. Graft survival time was observed. Some grafts were harvested for histopathological investigation on day 10 after transplantations. The levels of CD4+ and CD8+ T lymphocytes and the concentrations of interleukin 2(IL-2) and interferon (IFN)γ in peripheral blood were examined on day 10 after transplantations. At the same time, the body weight, the hepatic function, renal function and the haemoglobin of the recipients were also examined. The graft survival time of untreated group was 7.14 ± 1.07 days. Rapamycin group was 11.14 ± 1.35 days. Lef group was 11.29 ± 1.80 days. While in rapamycin + Lef group, the graft survival time was prolonged to 13.86 ± 1.57 days(P < 0.05). Histological changes of the allografts in rapamycin + Lef group were much milder than either of the two single drug groups. The absolute number and the percentage of CD4+ T lymphocytes in peripheral blood in rapamycin + Lef group were lower than those of rapamycin or Lef group on day 10 after transplantations(P < 0.05), while the percentage of CD8+ T lymphocytes in rapamycin + Lef group was higher than that of rapamycin or Lef group(P < 0.05). The absolute number of CD8+ T lymphocytes was not significantly different among rapamycin group, Lef group and rapamycin + Lef group. The levels of IL-2 and IFN-γ in rapamycin + Lef group were significantly lower than that of rapamycin group or Lef group(P < 0.05). The body weight, the hepatic function, renal function and the haemoglobin were not significantly different among rapamycin group, Lef group and rapamycin + Lef group (P > 0.05). Combined use of rapamycin and Lef had better effect on the prevention of acute cardiac allografts rejection in rats than monotherapy.

► We first combined rapamycin and leflunomide in preventing acute rejection in rat. ► Combining the two drugs prolonged the graft survival compared with single use. ► Combining the two drugs further lowered the level of CD4+ T lymphocytes. ► Combining the two drugs further lowered the levels of IL-2 and IFN-γ. ► The two drugs were additive in therapeutic effect.

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