title: Evaluation of interleukin-2 mRNA in whole blood as a parameter for monitoring cyclosporine pharmacodynamics.
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 real-time 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 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.
authors.affiliation: Department of Hospital Pharmacy, Nagoya University School of Medicine, Japan. t-kuzuya@med.nagoya-u.ac.jp
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kuzuya
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Akio
authors.initials: A
authors.lastname: Katayama
authors.forename: Takaharu
authors.initials: T
authors.lastname: Nagasaka
authors.forename: Yuko
authors.initials: Y
authors.lastname: Miwa
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Uchida
authors.forename: Akimasa
authors.initials: A
authors.lastname: Nakao
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada