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Open Access 01-12-2007 | Research

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

Authors: Abel Torres, Leslie Storey, Makala Anders, Richard L Miller, Barbara J Bulbulian, Jizhong Jin, Shalini Raghavan, James Lee, Herbert B Slade, Woubalem Birmachu

Published in: Journal of Translational Medicine | Issue 1/2007

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 ≥ 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.

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Title: Immune-mediated changes in actinic keratosis following topical treatment with imiquimod 5% cream
Authors: Abel Torres
Leslie Storey
Makala Anders
Richard L Miller
Barbara J Bulbulian
Jizhong Jin
Shalini Raghavan
James Lee
Herbert B Slade
Woubalem Birmachu
Publication date: 01-12-2007
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2007
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/1479-5876-5-7

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