Evaluation of interleukin-2 mRNA in whole blood as a parameter for monitoring cyclosporine pharmacodynamics

Takafumi Kuzuya, Takaaki Kobayashi, Akio Katayama, Takaharu Nagasaka, Yuko Miwa, Kazuharu Uchida, Akimasa Nakao, Kiyofumi Yamada

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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 languageEnglish
Pages (from-to)604-608
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume32
Issue number4
DOIs
Publication statusPublished - 04-2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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