Background Imiquimod 5% cream is a topically applied immune response modifier that has been shown to give effective treatment of actinic keratosis (AK). The therapeutic effects of imiquimod are likely to involve the provocation of a cutaneous immune response against abnormal cells, an assumption based on a strong correlation between complete clearance rates and the severity of the local skin reactions (erythema, oedema, erosion/ulceration, weeping/exudation and scabbing/crusting); however, no clinical studies have conclusively proved this mechanism.

Objectives To determine the nature of cellular infiltrates induced by the application of imiquimod to AK lesions and to study cells involved in the cutaneous immune response.

Methods Eighteen patients participated in this phase I, randomized, double‐blind, parallel group, vehicle‐controlled study. Enrolled patients were randomized in a 2 : 1 ratio to receive imiquimod cream or vehicle cream and applied study cream to five lesions on the scalp, forearm or upper trunk once daily, three days per week for up to 16 weeks. Each patient had punch biopsies of two distinct AK lesions: a lesion was biopsied before treatment to obtain baseline biomarker levels, and a different lesion was biopsied after 2 weeks of treatment. Biopsy specimens were examined using routine and immunohistochemical staining.

Results The imiquimod group showed statistically significant increases from baseline to week 2 in tissue biomarker levels for CD3, CD4, CD8, CD11c, CD86/CD11c, CD68, HLA‐DR and TUNEL. No significant differences were seen for the vehicle group. Complete clearance of all treated AK lesions was achieved in five of 11 (45%) imiquimod patients and in none of six vehicle patients.

Conclusions Imiquimod stimulates a cutaneous immune response characterized by increases in activated dendritic cells and CD4+ and CD8+ T cells.