Imiquimod: a potential role in dermatology?

Imiquimod, a heterocyclic imidazoquinoline amide (Fig. 1), is an immune response‐modifying drug that demonstrates potent antiviral and antitumour activity both in vitro and in vivo in animal and human studies.1, 2 Imiquimod's activity was discovered while screening drugs for antiherpesvirus activity.1 While imiquimod exhibits no direct antiviral or antiproliferative activity when examined in vitro in cell culture systems, its potent antiviral and antitumour activity is brought about by its ability to act as a potent immune response‐modifying agent.1 Imiquimod's activity comes through its ability to induce the production of cytokines, which in turn stimulate T cells, thereby enhancing innate and acquired cellular immunity.2 Imiquimod stimulates the immune system through the induction of interferon (IFN)‐α and other cytokines and the cellular arm of acquired immunity through the induction of IFN‐α, IFN‐γ and interleukin (IL)‐12. In the last 2 years, results have shown that cells of the immune response recognize pathogens by special pattern recognition receptors on the immune cell surface.3 These receptors are called Toll‐like receptors (TLRs) because they resemble the Toll receptors discovered in the fruit‐fly (Drosophila melanogaster). In humans, TLRs 1–10 have been identified. Imiquimod acts through TLR 7 and stimulates rapid synthesis and release of cytokines from monocyte, macrophage and dendritic cells. Imiquimod is the first small molecule disclosed to act through TLR activation, especially TLR 7.4 Although imiquimod itself does not directly stimulate T‐cell proliferation, cytokines such as IFN‐α, IL‐2 and IL‐12 are capable of stimulating the production of T‐helper type 1 (Th1) immune response.1 With the boosting of the Th1 response, it is therefore likely that skin conditions such as virus infections, or control and regression of tumours, can be affected by this immune modulation. Imiquimod has also been shown to inhibit the production of the T‐helper type 2 (Th2) cytokine IL‐5 in both mouse and human cell lines, thereby raising the possibility that imiquimod may be useful in atopic disease where an increase in Th1 response and decrease in Th2 response are required.1 With these actions on the immune system, imiquimod has the potential to be of use in a wide range of conditions including infections and neoplastic or immune‐mediated diseases.