Cellular requirements for cytokine production in response to the immunomodulators imiquimod and S-27609

摘要: Imiquimod (R-837) and its analog, S-27609, belong to a class of imidazoquinolinamines that have potent antitumor antiviral effects in animals. Much their biologic activity is result the induction cytokines, including interferon-alpha (IFN-alpha), tumor necrosis factor alpha (TNF), others. In this study, cells responsible for S-27609- imiquimod-induced cytokine production were characterized. E rosette+ T not major cell population IFN-alpha TNF response S-27609 or imiquimod. contrast, rosette- unseparated PBMC produced similar concentrations Elimination monocytes by treatment with lysosomotropic agent L-leucine methyl ester (LME) depletion using antibody CD14 immunomagnetic beads abrogated induced imiquimod, LPS but poly(I)/(C). LME also abolished interleukin (IL)-1 alpha, IL-beta, IL-6, IL-8 stimulated Removal HLA-DR+ CD36+ caused significant reduction TNF. B cells, NK dendritic did significantly reduce S-27609. Thus, majority release human imiquimod rosette-, CD14+, CD36+, monocyte.