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Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
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Changing the dosing schedule minimizes the disruptive effects of interferon on clock function

S Ohdo1, S Koyanagi, H Suyama

  • 1Department of Clinical Pharmacokinetics, Division of Pharmaceutical Sciences, Graduate School, Kyushu University, Higashi-Ku, Fukuoka, Japan. ohdo@phar.kyushu-u.ac.jp

Nature Medicine
|March 7, 2001
PubMed

Insights

Interferon-alpha disrupts the body's natural 24-hour rhythms, affecting clock genes and bodily functions. Optimizing drug dosing schedules can minimize these adverse effects and improve treatment outcomes.

Area of Science:

  • Chronobiology
  • Pharmacology
  • Molecular Biology

Background:

  • Drug efficacy and toxicity are influenced by the body's 24-hour rhythms.
  • Drugs can disrupt these circadian rhythms, leading to illness and altered homeostasis.
  • Mechanisms of drug-induced disruption of circadian clock genes are not well understood.

Purpose of the Study:

  • To investigate the disruptive effects of interferon-alpha on circadian rhythms.
  • To elucidate the impact of interferon-alpha on clock gene expression.
  • To explore strategies for mitigating drug-induced circadian disruption.

Main Methods:

  • Assessed locomotor activity and body temperature rhythms in response to interferon-alpha.
  • Measured clock gene mRNA expression in peripheral tissues and the suprachiasmatic nuclei.
  • Examined the effect of interferon-alpha on photic induction of the Per gene.

Main Results:

  • Interferon-alpha disrupted rhythms of activity, body temperature, and clock gene expression.
  • Rhythmicity of clock genes and photic Per gene induction in the suprachiasmatic nuclei were disturbed.
  • Optimizing dosing schedules can overcome alterations in clock function.

Conclusions:

  • Interferon-alpha significantly disrupts circadian rhythms and clock gene expression.
  • Circadian clock disruption represents a novel class of adverse drug effects.
  • Adjusting drug dosing schedules can minimize adverse effects and improve therapeutic outcomes.

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