Aldara
Dermal dendritic cells in anogenital warty lesions unresponsive to an immune-response modifier.

Arrese J, Paquet P, Claessens N, Pierard-Franchimont C, Pierard G.

Department of Dermatopathology University Medical Center Sart Tilman, Liege, Belgium.

BACKGROUND: Human papilloma viruses (HPV) are responsible for a variety of proliferative epithelial lesions including anogenital condylomas. These lesions may regress during treatment with an immune-response modifier such as imiquimod. The release of specific cytokines from the monocyte-macrophage lineage induces a cascade of events abating the HPV replication. METHOD: A total of 14 persistent warty anogenital lesions were excised 4 to 7 weeks after completing a 4-month imiquimod treatment. Another series of 25 untreated condylomas and 8 bowenoid papulosis served as controls. All examined lesions had been excised in otherwise healthy individuals with a normal immune status. Lesions were examined for the presence of Langerhans cells and subpopulations of the monocyte/macrophage/dendrocyte lineage using immunohistochemical detection of L1-protein, CD68, lysozyme and Factor-XIIIa. CD45R0-positive T lymphocytes were also identified. HPV capsid antigens and genotypes were searched for using immunohistochemistry and in situ hybridization, respectively. RESULTS: The persistent although treated anogenital lesions were identified as 10 viral condylomas, 3 bowenoid papulosis and 1 basal cell carcinoma. The inflammatory cell densities and distributions were similar in the untreated and imiquimod-resistant condylomas with the exception of Factor XIIIa-positive dendrocytes. These dermal dendritic cells were slim and rare in all imiquimod-resistant lesions. In contrast, about two-thirds of the untreated condylomas were enriched in these cells. CONCLUSION: As dermal dendritic cells play a role in the immune surveillance, their low densities in some lesions might be a key feature responsible for low cytokine local production and failure of imiquimod treatment. The combined apparent lack of Langerhans cell activation might suggest that both intraepidermal and intradermal compartments of antigen-presenting cells are affected in imiquimod-resistant lesions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11168764&dopt=Abstract imiquimod Aldara



Aldara
Imiquimod therapy for molluscum contagiosum.

Liota E, Smith KJ, Buckley R, Menon P, Skelton H.

Department of Dermatology, National Naval Medical Center, Bethesda, Maryland 20089-5600, USA.

BACKGROUND: Molluscum contagiosum virus (MCV) is a large double-stranded DNA virus that is a member of the family Poxviridae, and which has a worldwide distribution. As with other poxviruses, MCV does not appear to develop latency but evades the immune system through the production of viral specific proteins. Objective: To evaluate the therapeutic efficacy of imiquimod 5% cream for MCV. METHODS: Thirteen children >5 and <10 years old, 19 immune-competent adults and four adults with advanced, but stable HIV-1 disease with >10 MCV lesions were treated with topical 5% imiquimod cream three times weekly for up to 16 weeks. RESULTS: Fourteen of 19 immune-competent adults, four of four adults with HIV-1 disease, and six of 13 children had resolution of their MCV lesions in <16 weeks of imiquimod therapy. Children tended to have more pruritus and inflammatory reactions with imiquimod, although most treated lesions appeared to respond. The development of new MCV lesions resulted in a lower overall resolution of the lesions in children. Imiquimod appeared to be the most efficacious in patients with HIV-1 disease and in the genital area in immune-competent adults. CONCLUSION: Although topical imiquimod appears to have some efficacy in the therapy of MCV, in children the pruritus correlated relatively well with the development of new lesions. In adults, areas that would be expected to have better penetration appeared to respond more consistently. Although the HIV-1-positive patients had the largest clinical lesions at the onset of therapy, as a group they had the best overall response to therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11179929&dopt=Abstract imiquimod Aldara



Aldara
Bowen's disease (squamous cell carcinoma in situ) in immunosuppressed patients treated with imiquimod 5% cream and a cox inhibitor, sulindac: potential applications for this combination of immunotherapy.

Smith KJ, Germain M, Skelton H.

Department of Dermatology and Pathology, National Naval Medical Center, Bethesda, Maryland 20889-5600, USA. HSkelIII aol.com

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) often have a protracted course. However, all these patients are immunosuppressed and may have a high incidence of cutaneous malignancies. OBJECTIVE: To determine if combination therapy using topical imiquimod cream 5% and the oral cyclooxygenase (COX) inhibitor are useful in the therapy of squamous cell carcinoma in situ (SCC in situ)/Bowen's disease in patients with long-standing CLL. METHODS: Five CLL patients with head and neck cutaneous SCC in situ, which met criteria for Bowen's disease, were treated with topical 5% topical imiquimod cream and an oral COX inhibitor, sulindac 200 mg twice a day. RESULTS: All patients showed clinical resolution and histologic clearing of the tumors after 16 weeks of therapy. CONCLUSION: The local immune modulator, 5% imiquimod, in combination with a COX inhibitor, with its many potential antitumor effects may stimulate the innate and possibly the adaptive immune responses to clear these malignancies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11207687&dopt=Abstract imiquimod Aldara



Aldara
Imiqimod in clinical practice.

Trofatter KF Jr.

Mount Sinai Medical Center, Department of Obstetrics and Gynecology, 1 Mount Sinai Drive, Cleveland, Ohio, USA 44106-4198, USA.

Imiquimod 5% cream is a new compound which modifies the immune response by stimulating the production of interferon alpha and other cytokines. It has shown remarkable promise in the treatment of external genital and perianal warts when applied overnight, three times a week. It is also associated with a lower recurrence than those found with other current treatments. This paper reviews two of the pivotal multi-centre studies which confirm its efficacy in human papilloma virus (HPV) infections. These studies compared the effectiveness and safety of imiquimod 1% cream, imiquimod 5% cream and vehicle cream in the treatment of external anogenital warts.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10387959&dopt=Abstract imiquimod Aldara



Aldara
Identification of genes induced by a macrophage activator, S-28463, using gene expression array analysis.

Buates S, Matlashewski G.

Department of Microbiology and Immunology, McGill University, Montreal, Canada H3A 2B4.

S-28463 and imiquimod are imidazoquinoline compounds which stimulate microbicidal activity by inducing a local immune response at the site of application. Imiquimod-containing cream is an effective clinical treatment against cervical warts caused by human papillomavirus infection. Imiquimod also induces leishmanicidal activity both in vitro in macrophages and in vivo in a mouse model for cutaneous leishmaniasis. The major target cells of S-28463 and imiquimod are macrophages. To explore the molecular basis in which imidazoquinolines generate macrophage microbicidal activity, a cDNA gene array analysis was undertaken to identify genes induced by S-28463. Out of 588 genes screened in this assay, only 13 genes were significantly induced by S-28463. Remarkably, virtually all of the induced genes are involved in macrophage activation and inflammatory response. This experimental approach defines the mechanism of action of this clinically relevant compound in the induction of microbicidal activity in macrophages and also potentially identifies novel genes associated with microbicidal activity in this cell type.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11257027&dopt=Abstract imiquimod Aldara



Aldara
The immune response modifier resiquimod mimics CD40-induced B cell activation.

Bishop GA, Ramirez LM, Baccam M, Busch LK, Pederson LK, Tomai MA.

Department of Microbiology, VA Medical Center, Iowa City, Iowa 52242, USA. gail-bishop uiowa.edu

Members of the imidazoquinoline molecule family, including imiquimod and resiquimod (R-848), have potent antiviral and antitumor activities. Imiquimod cream (5%) (Aldara) is currently indicated for treatment of external genital and perianal warts. Previous characterization of these compounds has focused upon their ability to activate monocytes and dendritic cells, but recent studies have shown that resiquimod also stimulates B lymphocytes to proliferate and express an activated phenotype. This suggests that resiquimod could potentially serve as an effective vaccine adjuvant in stimulating a humoral immune response. This study shows that resiquimod mimics effects of the T-dependent CD40 signal in both mouse and human B cell lines. Resiquimod, like CD40, stimulates antibody secretion, cytokine production, protection from apoptosis, and CD80 upregulation. In addition, it shows synergy with signals delivered by the B cell antigen receptor and heightens CD40-mediated B cell activation, demonstrating that resiquimod can enhance antigen-specific responses in B lymphocytes. Copyright 2001 Academic Press.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11277614&dopt=Abstract imiquimod Aldara