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New insights into imiquimod’s mechanism of action

Recent research has uncovered aspects of the mechanism of action of imiquimod that were not previously understood, potentially revealing new targets for the treatment of inflammatory disease in the skin and elsewhere in the body. That’s according to findings published in Immunity (Oct. 18, 2016; 45(4):761–773).

The immunomodulator imiquimod has been used for the treatment of some forms of skin cancer and viral infections in the skin. However, the authors of the paper note in a press release from the Technical University of Munich (TUM) in Germany that in addition to triggering an immune response to abnormal cells, imiquimod also triggers NLRP3 inflammasome, which usually responds to tissue stress and cellular damage.

While this inflammatory response is valuable for fighting infection, when uncontrolled it can result in negative outcomes, the authors note. “We think that these other mechanisms of action of imiquimod might contribute to the efficacy or adverse side effects of the medication,” said Dr. Olaf Gross, group leader at the TUM Institute for Clinical Chemistry and Pathobiochemistry and senior author on the paper.

The investigators were able to show that imiquimod triggers the NLRP3 inflammasome by impairing the respiratory chain in mitochondria and thereby impairing the ability of the cell to power itself.

“There is a lot of excitement about generating new anti-inflammatory medications by targeting the NLRP3 inflammasome,” lead author Christina J. Gross PhD, said in the release. “We hope that our research will lead to the design of medications that can prevent dangerous hyperactivation of the NLRP3 inflammasome that may occur in diseases like gout and multiple sclerosis.”

Dr. Olaf Gross and his research team are following-up on their findings, investigating whether the effect of imiquimod on the mitochondria is the mechanism behind imiquimod’s inhibition of the growth of cancer cells.

They also plan to investigate compounds related to imiquimod to see if the different effects of the medication can be uncoupled.

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