Changing the dosing schedule minimizes the disruptive effects of interferon on clock function

Shigehiro Ohdo, Satoru Koyanagi, Hinako Suyama, Shun Higuchi, Hironori Aramaki

Research output: Contribution to journalArticlepeer-review

175 Citations (Scopus)

Abstract

The effectiveness and toxicity of many drugs vary depending on the relationship between the dosing schedule and the 24-hour rhythms of biochemical, physiological and behavioral processes. In addition, several drugs can cause alterations to the 24-hour rhythms leading to illness and altered homeostatic regulation. However, the mechanisms of this drug-based disruption of circadian 'clock' genes remain unclear. Here, we show the disruptive effect of interferon-α on the rhythm of locomotor activity, body temperature and clock-gene mRNA expression in the periphery and suprachiasmatic nuclei, a primary circadian pacemaker. The rhythmicity of clock genes and the photic induction of the Per gene in suprachiasmatic nuclei were disturbed by the repetitive administration of interferon-α. Moreover, alteration of clock function, a new concept of adverse effects, can be overcome by optimizing the dosing schedule to minimize adverse drug effects.

Original languageEnglish
Pages (from-to)356-360
Number of pages5
JournalNature medicine
Volume7
Issue number3
DOIs
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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