Evaluation of Interleukin-2 mRNA in Whole Blood as a Parameter for Monitoring Cyclosporine Pharmacodynamics(Pharmacology)

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Inhibition of cytokine production is the main immunosuppressive effect of cyclosporine (CsA), which is widely used in organ transplantation. Pharmacodynamic (PD) assay for evaluating the inhibition of interleukin-2 (IL-2) production for each patient could provide a more appropriate dosing regimen. We measured the suppression of IL-2 mRNA expression in whole blood following the addition of a range of CsA concentrations by a realtime reverse transcription-polymerase chain reaction (RT-PCR) method. Individual CsA sensitivity on the IL-2 mRNA expression was assessed with healthy subjects both in vitro and ex vivo. We also evaluated it in pre-transplant patients before taking immunosuppressive drugs. Sigmoid E_<max> model was used to analyze the relationship between CsA concentration and IL-2 mRNA expression. The assay was completed within 8h. The concentration that resulted in IC_<50> showed high reproducibility and specificity among the healthy subjects (p<0.005, n=5). Ex vivo study indicated similar inhibition profiles to those of in vitro studies (n=3). The values of IC_<50> obtained from patients (n=22) also showed large variations and were significantly lower than those from healthy subjects (p<0.05). Semi-quantitative RT-PCR was considered to be a rapid and reliable assay. Our data imply that measurement of IL-2 mRNA levels in whole blood could be valuable in monitoring CsA PD in transplant patients.
公益社団法人日本薬学会の論文
2009-04-01

Evaluation of Interleukin-2 mRNA in Whole Blood as a Parameter for Monitoring Cyclosporine Pharmacodynamics(Pharmacology)

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