Therapeutic index of methotrexate depends on circadian cycling of tumour necrosis factor-α in collagen-induced arthritic rats and mice

To, Hideto; Irie, Sadaharu; Tomonari, Mari; Watanabe, Yûko; Kitahara, Takashi; Sasaki, Hidetada

doi:10.1211/jpp.61.10.0009

Cited by 28 publications

(31 citation statements)

References 27 publications

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“…RA chronotherapy has been studied using glucocorticoid and benoxaprofen (16 -18). We also revealed that optimizing the dosing time of methotrexate, which is a disease-modifying antirheumatic drug that has been used to treat many RA patients, improved the symptoms of RA compared to the current standard dosing methods (19,20).…”

Section: Introductionmentioning

confidence: 99%

Dosing Time–Dependency of the Arthritis-Inhibiting Effect of Tacrolimus in Mice

et al. 2011

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Abstract. 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.

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Section: Introductionmentioning

confidence: 99%

Dosing Time–Dependency of the Arthritis-Inhibiting Effect of Tacrolimus in Mice

et al. 2011

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“…On the other hand, the arthritis scores of the ZT10 group did not significantly differ from those of the control group for the entire study period in mice. 26 In our previous studies using CIA model, MTX dosing groups showed no significant adverse effects such as myelosuppression. MTX is an anticancer drug, the administration of which is often associated with adverse effects such as myelosuppression.…”

Section: Disease-modifying Antirheumatic Drugs Methotrexatementioning

confidence: 79%

“…25 A previous study administered MTX once daily at Zeitgeber time (ZT) 10 or ZT22 and found that the arthritis score was significantly lower in the ZT22 group than in the control and ZT10 groups in rats with CIA ( Figure 1). 26 On day 22, the inhibition rate of the arthritis score in the ZT22 group was approximately fivefold higher than that in the ZT10 group. Moreover, plasma TNF-α levels were found to be 3.03-to 5.39-fold higher in mice with CIA than in normal mice at all sampling times after the onset of RA.…”

Section: Disease-modifying Antirheumatic Drugs Methotrexatementioning

confidence: 85%

Chronotherapy for rheumatoid arthritis: current perspectives

To¹

2016

CPT

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Rheumatoid arthritis (RA) is an autoimmune disorder of unknown etiology. Morning stiffness, a characteristic feature of RA, shows a 24-hour rhythm. Cytokines, which are considered to play an important role in the pathogenesis of RA, also exhibit a 24-hour rhythm, with a peak in the early morning. These rhythms have been attributed to the endogenous hormone balance and changes in expression levels of clock-related genes. Chronotherapy based on the 24-hour rhythm of RA has been performed using glucocorticoids and disease-modifying antirheumatic drugs. In a previous study, it was reported that modified-release prednisone tablets were administered to patients with RA at night, which demonstrated that the severity of morning stiffness was markedly less than that in patients receiving the standard treatment. Methotrexate (MTX) is the most frequently used RA drug worldwide. In a basic study, cytokines and inflammatory responses in RA model animals showed 24-hour rhythms, based on which MTX was administered and exerted dosing time-dependent antirheumatic effects. Plasma C-reactive protein and cytokine levels also exhibit 24-hour rhythms in patients with RA, with peaks occurring in the early morning. MTX has been shown to markedly inhibit the exacerbation of arthritis in patients with RA when it is administered as inflammatory responses and tumor necrosis factor-α levels begin to increase. Tacrolimus (TAC) is an immunosuppressive agent that is administered to patients who undergo organ transplants. Since one of the mechanisms of action of TAC is the inhibition of inflammatory cytokine production, it is used as an RA therapeutic drug. When TAC was previously administered in the early light or early dark phase to RA model animals, the group treated in the early light phase had notably inhibited increase in arthritis scores compared with that in the early dark phase. The selection of an optimal dosing time associated with 24-hour rhythms in RA symptoms may lead to more effective and safer treatments for RA using glucocorticoids and disease-modifying antirheumatic drugs.

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“…In previous studies, we revealed that the circadian rhythms of SAA and TNF- levels, which peak in the light phase, were maintained after RA onset in CIA and MRL/lpr mice ( Fig. 6 and 9; To et al, 2009 and2011). Based on the circadian rhythms of plasma SAA and TNF- levels in MRL/lpr mice (Fig.…”

Section: Basic Studymentioning

confidence: 83%

“…In the CIA model, clear circadian rhythms in SAA and TNF-levels were observed, with higher levels seen in the morning and lower levels observed at night ( Fig. 6; To et al, 2009), and MTX was intraperitoneally injected at 5:00 or 17:00 every 7 days for 3 weeks. The 5:00-treated group displayed significantly reduced arthritis scores compared with the control and 17:00-treated groups (P < 0.01, respectively; Fig.…”

Section: Basic Studymentioning

confidence: 95%

Chronobiology of and Chronotherapy for Rheumatoid Arthritis

To¹

2011

Autoimmune Disorders - Current Concepts and Advances From Bedside to Mechanistic Insights

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Therapeutic index of methotrexate depends on circadian cycling of tumour necrosis factor-α in collagen-induced arthritic rats and mice

Abstract: Our findings suggest that choosing an optimal dosing time associated with the 24-h cycling of TNF-alpha could lead to effective treatment of rheumatoid arthritis by methotrexate.

Cited by 28 publications

References 27 publications

Dosing Time–Dependency of the Arthritis-Inhibiting Effect of Tacrolimus in Mice

Dosing Time–Dependency of the Arthritis-Inhibiting Effect of Tacrolimus in Mice

Chronotherapy for rheumatoid arthritis: current perspectives

Chronobiology of and Chronotherapy for Rheumatoid Arthritis

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