title: A single administration of recombinant human interleukin-12 is associated with increased expression levels of interferon-gamma and signal transducer and activator of transcription in healthy subjects.
abstract: The objectives of this study were to assess the safety and tolerability of single doses of 1, 4, and 8 mug of recombinant human interleukin-12 (rhIL-12) administered subcutaneously to healthy subjects. The pharmacokinetics, pharmacodynamics, and pharmacogenomics of rhIL-12 were evaluated. Recombinant human IL-12 was well tolerated in these healthy male and female subjects. The most frequently reported adverse events were flu-like symptoms, which exhibited a dose-response relationship. Pharmacokinetic analysis suggested that serum IL-12 levels increased with dose. Analysis of serum levels indicated that interferon-gamma increased with the dose of rhIL-12, whereas IL-6 levels showed no changes with rhIL-12 treatment. The messenger ribonucleic acid expression of signal transducer and activator of transcription was significantly increased 24 hours after the administration of rhIL-12 for all dose groups versus placebo, and results indicated that the magnitude of increase may be dose dependent. This study suggests that interferon-gamma and signal transducer and activator of transcription are biomarkers of rhIL-12 activity.
authors.affiliation: Experimental Medicine, Wyeth Research, 35 Cambridge Park Drive, Cambridge, MA 02140, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Trudeau
authors.forename: Monette M
authors.initials: MM
authors.lastname: Cotreau
authors.forename: Lucille
authors.initials: L
authors.lastname: Stonis
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Dykstra
authors.forename: Judy L
authors.initials: JL
authors.lastname: Oestreicher
authors.forename: Andrew
authors.initials: A
authors.lastname: Strahs
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dorner
authors.forename: Victor H
authors.initials: VH
authors.lastname: Van Cleave
authors.forename: William L
authors.initials: WL
authors.lastname: Trepicchio
authors.forename: Ullrich S
authors.initials: US
authors.lastname: Schwertschlag
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics*; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000097:blood / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D010597:Pharmacogenetics / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase