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Topical Immune Response Modifiers: Adjuvants

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Clinical and Basic Immunodermatology

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Abstract

Imiquimod and ingenol mebutate are topical treatments widely utilized for their anti-tumor effects on actinic keratosis (AK). In addition to their anti-tumor effects, both topical medications are reported to be effective as off-label alternatives to treat various viral, inflammatory, and malignant skin conditions.

Imiquimod is a topical immune modulator approved for the treatment of actinic keratoses, anogenital warts, and superficial basal cell carcinomas. Imiquimod exhibits anti-viral and anti-tumor effects by stimulating both the innate and adaptive immune responses via toll-like receptors (TLR). TLRs on antigen presenting cells induce the production of T-helper-1 cytokines leading to malignant cell death. The dosage, application, and duration depend on the condition being treated. The medication is largely well-tolerated, with application site reactions expected.

Ingenol mebutate is derived from the sap of the Euphorbia peplus plant. It has a dual mechanism of action comprised of initial rapid cell death followed by an acute inflammatory response. It is available as a topical gel and is administered over 2–3 days and has a favorable safety profile, making it an appealing alternative to other spot and field therapies.

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Author information

Authors and Affiliations

  1. Department of Dermatology, Mount Sinai School of Medicine, One Gustave Levy Place, 1047, New York, NY, 10029, USA

    Annemarie Uliasz MD

  2. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Mark G. Lebwohl MD

Authors
  1. Annemarie Uliasz MD
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  2. Mark G. Lebwohl MD
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Corresponding author

Correspondence to Annemarie Uliasz MD .

Editor information

Editors and Affiliations

  1. School of Medicine, University of Maryland Baltimore, Baltimore, Maryland, USA

    Anthony A. Gaspari

  2. Department of Dermatology, University of Texas Health Science Center, Houston, Texas, USA

    Stephen K. Tyring

  3. Department of Dermatology and Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Daniel H. Kaplan

Questions

Questions

  1. 1.

    Which of the following best describes the mechanism of action of imiquimod?

    1. A.

      blocks synthesis of the pyrimidine thymidine, which is a nucleoside required for DNA replication

    2. B.

      competitively inhibits and inactivates HSV-specified DNA polymerases preventing further viral DNA synthesis without affecting the normal cellular processes

    3. C.

      it produces an innate immune response via its action as a toll-like receptor (TLR) agonist

    4. D.

      Following an initial cell necrosis, protein kinase c is activated resulting in the release of pro-inflammatory cytokines, tumor-specific antibodies, an endothelial adhesion molecule expression, and a substantial infiltration of neutrophils which generate tumoricidal reactive oxygen intermediates

  2. 2.

    Which of the following statements is false?

    1. A.

      imiquimod has been shown to be more effective and produce a less severe local skin reaction than 5-fluorouracil (5-FU)

    2. B.

      imiquimod is FDA approved to treat molluscum contagiousum

    3. C.

      The most common side effect of ingenol mebutate are application-site reactions

    4. D.

      Imiquimod possesses the unique capacity to uncover and treat sub-clinical actinic kersatoses

  3. 3.

    Which of the following best describes the mechanism of action of ingenol mebutate?

    1. A.

      Following an initial cell necrosis, protein kinase c is activated resulting in the release of pro-inflammatory cytokines, tumor-specific antibodies, an endothelial adhesion molecule expression, and a substantial infiltration of neutrophils which generate tumoricidal reactive oxygen intermediates

    2. B.

      a MyD88-dependent signaling cascade2 acts to recruit protein kinases and transcription factors, resulting in activation of nuclear factor-kβ (NF-kβ) that, upon activation, migrates to the nucleus and up-regulates the production of local pro-inflammatory cytokines

    3. C.

      blocks synthesis of the pyrimidine thymidine, which is a nucleoside required for DNA replication

    4. D.

      choices A + B

    5. E.

      none of the above

Answers

  1. 1.

    C

  2. 2.

    B

  3. 3.

    A

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Uliasz, A., Lebwohl, M.G. (2017). Topical Immune Response Modifiers: Adjuvants. In: Gaspari, A., Tyring, S., Kaplan, D. (eds) Clinical and Basic Immunodermatology. Springer, Cham. https://doi.org/10.1007/978-3-319-29785-9_45

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