Abstract
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-trans- plant 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 8 h. 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.
Original language | English |
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Pages (from-to) | 604-608 |
Number of pages | 5 |
Journal | Biological and Pharmaceutical Bulletin |
Volume | 32 |
Issue number | 4 |
DOIs | |
Publication status | Published - 04-2009 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Pharmacology
- Pharmaceutical Science