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

S Ohdo, S Koyanagi, H Suyama, S Higuchi… - Nature medicine, 2001 - nature.com
S Ohdo, S Koyanagi, H Suyama, S Higuchi, H Aramaki
Nature medicine, 2001nature.com
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 …
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.
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