Topical immunomodulation in dermatology: potential of toll-like receptor agonists

Topical immunomodulators include both immunostimulatory and immunosuppressive agents. If successful, topical immunotherapy may represent an important improvement in the therapy of inflammatory dermatoses, viral infections, and cancers of the skin and genital mucosa. Topical immunotherapy using obligate contact sensitizers such as diphencyprone or dinitrochlorobenzene has been used against viral (e.g., common warts) and autoimmune diseases (e.g., alopecia areata).

Newer agents such imidazoquinolines (imiquimod and resiquimod) act by cytokine secretion from monocytes/macrophages (interferon-alpha, interleukin-12, tumor-necrosis factor-alpha). The locally generated immune milieu leads to a Th1-dominance and cell-mediated immunity that have been clinically used to treat viral infections such as human papillomavirus, herpes simplex virus, and mollusca. Although these agents improve antigen presentation by dendritic cells, they also act on B cells leading to the synthesis of antibodies such as IgG2a. We have also introduced this treatment against cancerous lesions including initial squamous cell and basal cell carcinoma in immunocompetent and immunosuppressed patients. We provide examples of successful treatment of squamous cell cancer using topical imiquimod.

The available and additional Toll-like receptor agonists will help to improve the specific dermatologic therapy. Topical immunotherapy with both immunostimulatory and immunosuppressive agents bears potential for effective and patient friendly treatment of inflammatory, infectious, and cancerous skin diseases. Long-term evaluation will define the tolerability and safety profile of these novel topical agents.