Induction of interferon and other cytokines by imiquimod and its hydroxylated metabolite R-842 in human blood cells in vitro.
The low-molecular-weight immunomodulator drug candidate, imiquimod (R-837), and its hydroxylated metabolite R-842, induce interferon-alpha (IFN-alpha) in human blood cells in vitro when tested in concentrations of 0.5 microgram/ml or more. The amounts of IFN-alpha found increased with time from 2-6 h of incubation up to 24-48 h, and were dependent on cell number and drug concentration. These two chemicals yielded more IFN-alpha in human peripheral blood mononuclear cell (PBMC) cultures than other known inducers tested in parallel. They also induced detectable amounts of interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor-alpha in human PBMC cultures in vitro.
Weeks
C E
CE
3M Pharmaceuticals, Department of Pharmacology, 3M Center, St. Paul, MN 55144.
Gibson
S J
SJ
D000634:Aminoquinolines / Q000494:pharmacology*; D002452:Cell Count; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D006878:Hydroxides; D000077271:Imiquimod; D007369:Interferon Inducers / Q000494:pharmacology*; D016898:Interferon-alpha / Q000096:biosynthesis*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology*
D000634:Aminoquinolines; D016207:Cytokines; D006878:Hydroxides; D007369:Interferon Inducers; D016898:Interferon-alpha; C089168:4-amino-alpha,alpha-dimethyl-1H-imidazo(4,5-c)quinolin-1-ethanol; D000077271:Imiquimod