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Imiquimod: mode of action
Author(s) -
Schön M.P,
Schön M
Publication year - 2007
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2007.08265.x
Subject(s) - imiquimod , immunology , immune system , chemokine , receptor , mechanism of action , innate immune system , tlr7 , medicine , cancer research , pharmacology , biology , toll like receptor , in vitro , biochemistry
Summary Objective Since imiquimod, a nucleoside analogue of the imidazoquinoline family, has shown efficacy against many tumour entities, its mode of action has become a focus of scientific interest. Results The major biologic effects of imiquimod are mediated through agonistic activity towards toll‐like receptors (TLR) 7 and 8, and consecutively, activation of nuclear factor‐kappa B (NF‐κB). The result of this activity is the induction of pro‐inflammatory cytokines, chemokines and other mediators leading to activation of antigen‐presenting cells and other components of innate immunity and, eventually, the mounting of a profound T‐helper (Th1)‐weighted antitumoral cellular immune response. Several secondary effects on the molecular and cellular level may also be explained, at least in part, by the activation of NF‐κB. Moreover, independent of TLR‐7 and TLR‐8, imiquimod appears to interfere with adenosine receptor signalling pathways, and the compound causes receptor‐independent reduction of adenylyl cyclase activity. This novel mechanism may augment the pro‐inflammatory activity of the compound through suppression of a negative regulatory feedback mechanism which normally limits inflammatory responses. Finally, imiquimod induces apoptosis of tumour cells at higher concentrations. The pro‐apoptotic activity of imiquimod involves caspase activation and appears to depend on B cell lymphoma/leukemia protein (Bcl)‐2 proteins. Conclusions Overall, imiquimod acts on several levels, which appear to synergistically underlie the profound antitumoral activity of the compound.