title: Relationship between 24-hour rhythm in antiviral effect of interferon-beta and interferon-alpha/beta receptor expression in mice.
abstract: 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.
authors.affiliation: Clinical Pharmacokinetics, Division of Clinical Pharmacy, Department of Medico-Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takane
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Ohdo
authors.forename: Reiji
authors.initials: R
authors.lastname: Baba
authors.forename: Satoru
authors.initials: S
authors.lastname: Koyanagi
authors.forename: Eiji
authors.initials: E
authors.lastname: Yukawa
authors.forename: Shun
authors.initials: S
authors.lastname: Higuchi
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D002940:Circadian Rhythm; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007031:Hypothalamus / Q000378:metabolism; D007275:Injections, Intravenous; D016899:Interferon-beta / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000998:Antiviral Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D015088:2',5'-Oligoadenylate Synthetase