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.
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.
Trudeau
Caroline
C
Experimental Medicine, Wyeth Research, 35 Cambridge Park Drive, Cambridge, MA 02140, USA.
Cotreau
Monette M
MM
Stonis
Lucille
L
Dykstra
Kevin H
KH
Oestreicher
Judy L
JL
Strahs
Andrew
A
Dorner
Andrew J
AJ
Van Cleave
Victor H
VH
Trepicchio
William L
WL
Schwertschlag
Ullrich S
US
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
D015415:Biomarkers; D015850:Interleukin-6; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase