Dosing time-dependency of the arthritis-inhibiting effect of tacrolimus in mice

Kayo Obayashi, Mari Tomonari, Hiromichi Yoshimatsu, Ryuji Fukuyama, Ichiro Ieiri, Shun Higuchi, Hideto To

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Stiffness and cytokine in blood levels show 24-h rhythms in rheumatoid arthritis (RA) patients. We previously revealed that higher therapeutic effects were obtained in RA patients and RA model animals when the dosing time of methotrexate was chosen according to the 24-h rhythms to cytokine. In this study, we examined whether a dosing time-dependency of the therapeutic effect of tacrolimus (TAC) could be detected in collagen-induced arthritis (CIA) and MRL/lpr mice. To measure the levels of cytokines and serum amyloid A (SAA), blood was collected from CIA mice at different times. TAC was administered at two different dosing times based on these findings and its effects on arthritis and toxicity were examined. Plasma tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and SAA concentrations showed obvious 24-h rhythms with higher levels during the light phase and lower levels during the dark phase after RA crisis. The arthritis score and leukocyte counts were significantly lower in the group treated at 2 h after the light was turned on (HALO) than in the control and 14 HALO-treated groups. Our findings suggest that choosing an optimal dosing time could lead to the effective treatment of RA by TAC.

Original languageEnglish
Pages (from-to)264-273
Number of pages10
JournalJournal of Pharmacological Sciences
Issue number3
Publication statusPublished - Jul 21 2011


All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Obayashi, K., Tomonari, M., Yoshimatsu, H., Fukuyama, R., Ieiri, I., Higuchi, S., & To, H. (2011). Dosing time-dependency of the arthritis-inhibiting effect of tacrolimus in mice. Journal of Pharmacological Sciences, 116(3), 264-273.