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 mu g/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.