Induction of Interferon and Other Cytokines by Imiquimod and Its Hydroxylated Metabolite R-842 in Human Blood Cells In Vitro

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Abstract
The low-molecular-weight immunomodulator drug candidate, imiquimod (R-837), and its hydroxylated metabolite R-842, induce interferon-α (IFN-α) in human blood cells in vitro when tested in concentrations of 0.5 μg/ml or more. The amounts of IFN-α 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-α 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-α in human PBMC cultures in vitro.