Mechanism of Action and Emerging Role of Immune Response Modifier Therapy in Dermatologic Conditions

Abstract

Immune response modifiers (IRMs) are agents that target the body's immune system (i.e., cytokines, receptors, and inflammatory cells) to combat disease. Topical IRM therapies, which encompass both proinflammatory and immunosuppressive therapeutics, have been used to successfully treat a number of dermatologic conditions. Proinflammatory treatments include Toll-like receptor agonists (e.g., imiquimod 5% cream) and interferon (e.g., interferon-alpha) therapies, which have been used in the treatment of external genital warts, basal cell carcinoma, and other dermatologic diseases. Immunosuppressive therapies include topical and intralesional corticosteroids, anti-tumor necrosis factor agents (e.g., infliximab and etanercept), and anti-CD4+ T-cell agents, including calcineurin inhibitors and mycophenolate. These agents have been used to treat a number of conditions, including atopic and seborrheic dermatitis and psoriasis. This article reviews the mechanism of action of IRMs and the application of IRMs in several dermatologic diseases.

Generalized psoriasis induced by topical treatment of actinic keratosis with imiquimod

“…Imiquimod [1‐(2‐methylpropyl)‐1, H‐imidazo(4,5‐c), quinolin‐4‐amine] is an immune response modifier which activates immune cells via toll‐receptor (TLC) 7, initiating a cascade that leads to the induction of cytokines such as IFN‐alfa, gamma and IL‐12, which promote a Th‐1 immune response. These cytokines are capable of inducing psoriasis 8,9 . Evidence that psoriasis is an immune‐mediated disorder comes from laboratory studies, clinical observation, and use of targeted therapies 10 .…”

Treatment of basal cell carcinoma of the eyelids with 5% topical imiquimod: a 3-year follow-up study

“…In another study, 5% imiquimod was applied to the eyelids with good results in terms of clearance, but the authors state that the excellent recurrence rate was tentative because of the short-term follow-up time [5]. Imiquimod is one of a new class of immune response modifiers being used for various dermatological conditions [6]. The mechanism of action of imiquimod cream in treating BCC lesions is unknown, although it has been suggested that it may increase the infiltration of lymphocytes, dendritic cells and macrophages into the tumour lesion [7].…”

Expression of Epidermal CAMP Changes in Parallel with Permeability Barrier Status

“…The immune response modifier, imiquimod (IMQ), acts through two members of the toll-like receptor (TLR) family, TLR7 and/or 8, which recognize microbial pathogens or their metabolic products, and function as primary sensors of the innate immune system (Ambach, A, et al , 2004, Sauder, DN, 2004, Lai, Y, et al , 2008). These TLR are cell surface receptors that, when activated, stimulate production of epidermis-derived, interferon-alpha, tumour necrosis factor, and interleukin-1α (Sauder, DN, 1990, Barland, CO, et al , 2004, McInturff, JE, et al , 2005, Takeuchi, O, et al , 2009).…”