Imiquimod inhibits the differentiation but enhances the maturation of human monocyte-derived dendritic cells.
Imiquimod is a topically used immune response modifier effective in the treatment of genital warts caused by HPV. Its therapeutic effects are believed to be the release of proinflammatory cytokines from the monocyte-macrophage lineage resulting in a cascade of events abating the HPV replication. Dendritic cell maturation and activation have also been found to be induced by imiquimod. We hypothesized that imiquimod may promote the development of DC at all levels of their life cycle. In this study, in vitro cultured monocyte-derived dendritic cells (MoDC) were used to evaluate the effect of imiquimod regarding the modulation of DC differentiation, terminal maturation and their function by phenotypic cell surface molecules expression, cytokine secretion and T cell stimulation in allogeneic system. We demonstrate that imiquimod exerts differential effects on DC biology at different stages of DC development. It inhibits the differentiation of DC, which may indicate a more potent antigen uptake activity. DC maturation is induced by imiquimod with an enhanced antigen presenting activity and IL-12 production. These evidence might be relevant with the clinically proven effectiveness of imiquimod in the treatment of genital warts.
Zhu
Ke-Jian
KJ
Department of Dermatology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.
Cen
Jian-Ping
JP
Lou
Jun-Xiao
JX
Wang
Qi
Q
Zhang
Xing
X
Xu
Yan
Y
Chen
Xian-Zhen
XZ
Cheng
Hao
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000634:Aminoquinolines / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D000077271:Imiquimod; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D018664:Interleukin-12; D000077271:Imiquimod