Immune-mediated changes in actinic keratosis following topical treatment with imiquimod 5% cream

J Transl Med. 2007 Jan 26;5:7. doi: 10.1186/1479-5876-5-7.

Abstract

Background: The objective of this study was to identify the molecular processes responsible for the anti-lesional activity of imiquimod in subjects with actinic keratosis using global gene expression profiling.

Methods: A double-blind, placebo-controlled, randomized study was conducted to evaluate gene expression changes in actinic keratosis treated with imiquimod 5% cream. Male subjects (N = 17) with > or = 5 actinic keratosis on the scalp applied placebo cream or imiquimod 3 times a week on nonconsecutive days for 4 weeks. To elucidate the molecular processes involved in actinic keratosis lesion regression by imiquimod, gene expression analysis using oligonucleotide arrays and real time reverse transcriptase polymerase chain reaction were performed on shave biopsies of lesions taken before and after treatment.

Results: Imiquimod modulated the expression of a large number of genes important in both the innate and adaptive immune response, including increased expression of interferon-inducible genes with known antiviral, anti-proliferative and immune modulatory activity, as well as various Toll-like receptors. In addition, imiquimod increased the expression of genes associated with activation of macrophages, dendritic cells, cytotoxic T cells, and natural killer cells, as well as activation of apoptotic pathways.

Conclusion: Data suggest that topical application of imiquimod stimulates cells in the skin to secrete cytokines and chemokines that lead to inflammatory cell influx into the lesions and subsequent apoptotic and immune cell-mediated destruction of lesions.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adaptive Immunity / drug effects
  • Adaptive Immunity / genetics
  • Adjuvants, Immunologic / pharmacology
  • Administration, Topical
  • Aged
  • Aged, 80 and over
  • Aminoquinolines / administration & dosage*
  • Aminoquinolines / therapeutic use*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Proliferation / drug effects
  • Chemokines / genetics
  • Chemokines / metabolism
  • Demography
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Dosage Forms
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Humans
  • Imiquimod
  • Immunity, Innate / drug effects
  • Immunity, Innate / genetics
  • Interferon Type I / pharmacology
  • Keratosis, Actinic / drug therapy*
  • Keratosis, Actinic / genetics
  • Keratosis, Actinic / immunology*
  • Keratosis, Actinic / pathology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Receptors, Pattern Recognition / metabolism
  • Reproducibility of Results
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Adjuvants, Immunologic
  • Aminoquinolines
  • Chemokines
  • Dosage Forms
  • Interferon Type I
  • Receptors, Pattern Recognition
  • Imiquimod