Immunosuppressive therapy for prevention of acute rejection episode occasionally causes serious adverse effects, and thus it is important to develop new therapeutic approach for renal transplant recipients. This study evaluated the immunosuppressive pharmacodynamics of tetrandrine (TET) and/or methylprednisolone (MP) in haemodialysis patients in vitro by using the peripheral blood mononuclear cells (PBMCs) isolated from whole blood of haemodialysis patients. The median (range) of MP IC values against the proliferation of patients PBMCs was 7.04 (2.30-500.00) ng/mL. In contrast, the median (range) of MP IC values against the proliferation of healthy PBMCs was 4.44 (3.19-5.08) ng/mL. The median (range) of TET IC values against the proliferation of patients PBMCs was 1.61 (1.04-4.79) μmol/L. Lower concentrations of TET (0.3-300 nmol/L) were able to decrease the IC values of MP and thus potentiate the MP immunosuppressive effect on patient PBMCs. The median (range) of MP IC values in combination with 0.3, 3, 30, and 300 nmol/L TET were 0.92 (0.49-8.39), 2.10 (0.45-20.00), 0.35 (0.092-1.05), and 0.14 (0.05-6.78) ng/mL, respectively. TET potentiates the MP immunosuppressive pharmacodynamics and thus, it was possible to use the combination of MP and TET to attenuate MP side effects. There were significant correlations between the IC values of TET and stimulation indices (P=0.04, r=.58), the IC values of TET and the haemodialysis periods (P=0.04, r=.57), or the IC values of MP combined with 0.3 nmol/L TET and C-reactive protein concentrations (P=0.04, r=.64), respectively.
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http://dx.doi.org/10.1111/1440-1681.12797 | DOI Listing |
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