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

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.