Imiquimod: mode of action

Br J Dermatol. 2007 Dec;157 Suppl 2:8-13. doi: 10.1111/j.1365-2133.2007.08265.x.

Abstract

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-kappaB). 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-kappaB. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aminoquinolines / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • B-Lymphocytes / drug effects
  • Humans
  • Imiquimod
  • Immunity, Cellular / drug effects
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Receptors, Purinergic P1 / drug effects
  • Signal Transduction / drug effects
  • Toll-Like Receptors / agonists

Substances

  • Aminoquinolines
  • Antineoplastic Agents
  • Receptors, Purinergic P1
  • Toll-Like Receptors
  • Imiquimod