Relationship between 24-hour rhythm in antiviral effect of interferon-beta and interferon-alpha/beta receptor expression in mice

Jpn J Pharmacol. 2002 Dec;90(4):304-12. doi: 10.1254/jjp.90.304.


The influence of interferon-beta (IFN-beta) dosing time on antiviral activity was investigated in ICR male mice under light-dark cycle conditions (lights on at 07:00, off at 19:00) with food and water available ad libitum. There was a significant dosing time-dependent change in 2',5'-oligoadenylate synthetase (2',5'-OAS) activities, as an index of antiviral activity, in liver at 12 h after IFN-beta (15 MIU/kg, i.v.) injection. IFN-beta-induced 2',5'-OAS activity was more potent after the drug injection during the late dark phase. The higher antiviral effect of IFN-beta was observed when the interferon-alpha/beta receptor (IFNAR) expression in the liver increased, and the lower effect was observed when its expression decreased. IFN-beta-induced fever was more serious after IFN-beta injection from the late dark phase to the early light phase. A significant dosing time-dependent change was demonstrated for plasma IFN-beta concentrations, which showed a higher level during the light phase and a lower level during the dark phase. The dosing time-dependent change of plasma IFN-beta concentrations was not associated with that of the antiviral effect or fever induced by IFN-beta. These results suggest that selecting the most suitable dosing time of IFN-beta, associated with the 24-h rhythm of IFNAR expression in the liver, may be important to increase effectively the antiviral activity of the drug in experimental and clinical situations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / metabolism
  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / blood
  • Antiviral Agents / pharmacology*
  • Body Temperature / drug effects
  • Circadian Rhythm*
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Hypothalamus / metabolism
  • Injections, Intravenous
  • Interferon-beta / administration & dosage
  • Interferon-beta / blood
  • Interferon-beta / pharmacology*
  • Isoenzymes / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred ICR
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • RNA, Messenger / metabolism
  • Receptor, Interferon alpha-beta
  • Receptors, Interferon / drug effects*
  • Receptors, Interferon / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction


  • Antiviral Agents
  • Isoenzymes
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Interferon
  • Receptor, Interferon alpha-beta
  • Interferon-beta
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, mouse
  • 2',5'-Oligoadenylate Synthetase