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Immunosuppressive efficacy of tetrandrine combined with methylprednisolone against mitogen‐activated peripheral blood mononuclear cells of haemodialysis patients
Author(s) -
Xu Wencheng,
Meng Kehan,
Kusano Junichi,
Matsuda Hiroto,
Hara Yoshikazu,
Fujii Yoshiaki,
Suzuki Shinya,
Ando Eiki,
Wang Xiaoqin,
Tu Yuanchao,
Tanaka Sachiko,
Sugiyama Kentaro,
Yamada Haruki,
Hirano Toshihiko
Publication year - 2017
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12797
Subject(s) - tetrandrine , peripheral blood mononuclear cell , methylprednisolone , medicine , pharmacodynamics , pharmacology , hemodialysis , adverse effect , whole blood , in vitro , immunology , gastroenterology , pharmacokinetics , chemistry , biochemistry
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 50 values against the proliferation of patients PBMCs was 7.04 (2.30‐500.00) ng/mL. In contrast, the median (range) of MP IC 50 values against the proliferation of healthy PBMCs was 4.44 (3.19‐5.08) ng/mL. The median (range) of TET IC 50 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 50 values of MP and thus potentiate the MP immunosuppressive effect on patient PBMCs. The median (range) of MP IC 50 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 50 values of TET and stimulation indices ( P =0.04, r =.58), the IC 50 values of TET and the haemodialysis periods ( P =0.04, r =.57), or the IC 50 values of MP combined with 0.3 nmol/L TET and C‐reactive protein concentrations ( P =0.04, r =.64), respectively.