Aldara
Molecular analysis of the effect of topical imiquimod treatment of HPV 2/27/57-induced common warts.

Jacobs S, Grussendorf-Conen EI, Rosener I, Rubben A.

Department of Dermatology, University Hospital of the RWTH Aachen, Aachen, Germany.

Imiquimod is effective in the treatment of genital warts and clinical studies suggest activity against common warts as well. We have analyzed the effect of topical imiquimod on gene expression and virus load in human papilloma virus (HPV) 2/27/57-induced common warts. mRNA was extracted from keratinocyte culture, from normal skin, from three untreated common warts and from three common warts treated topically with 5% imiquimod cream twice daily. Differential gene expression was demonstrated by RT-PCR and by cDNA microarray hybridization. We further analyzed viral DNA content in scales from three superficially pared imiquimod-treated warts by real-time PCR. Comparison of normal skin with wart tissue revealed that HPV 2/27/57 infection led to an induction of IL-6, IL-10 and interferon-gamma inducible protein (IP10) and to an up-regulation of TGF-beta. We could further detect expression of PCTAIRE-3, WNT2B, frizzled-3, notch-2, notch-4 and BRCA2 in normal skin and common warts. Analysis of imiquimod-treated warts demonstrated that imiquimod enhanced IL-6 expression and induced IL-8, GM-CSF, MRP-8 and MRP-14. It could also be shown that imiquimod led to an infiltration of wart tissue with macrophages and to a strong decrease of viral copy number in warts within 3 months of treatment. Our data thus provide molecular proof of principle for imiquimod treatment of cutaneous common warts. 2004 S. Karger AG, Basel

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15452412&dopt=Abstract imiquimod Aldara



Aldara
The immune response modifiers imiquimod and R-848 are potent activators of B lymphocytes.

Tomai MA, Imbertson LM, Stanczak TL, Tygrett LT, Waldschmidt TJ.

Department of Pharmacology, 3M Pharmaceuticals, 3M Center, St. Paul, Minnesota 55144, USA.

Imiquimod and R-848 are members of a family of immune response modifiers that stimulate cytokine production in monocyte/macrophages and dendritic cell cultures. This study evaluated the effects of the imidazoquinolines, imiquimod and R-848, on B lymphocyte activation. Both agents induced proliferation of murine T-cell-depleted and highly purified splenic B cell preparations as well as purified human B cells. Resting and activated B cells responded to these agents, with activated cells responding more efficiently. B cells from the LPS-hyporesponsive C3H/HeJ mice and guanosine-hyporesponsive SJL mice proliferated in response to imiquimod and R-848, indicating a different mechanism of action than lipopolysaccharide and guanine nucleosides. B cells were also stimulated by imiquimod and R-848 to produce increased immunoglobulin levels. Increased expression of a number of B cell activation markers were seen following imiquimod or R-848 stimulation. Finally, R-848 was shown to act as a vaccine adjuvant enhancing OVA-specific IgG2a levels while suppressing total IgE. These results indicate that R-848 and imiquimod are potent activators of B lymphocytes and are capable of augmenting antigen-specific immunoglobulin production. Copyright 2000 Academic Press.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10915562&dopt=Abstract imiquimod Aldara



Aldara
Imiquimod induced regression of clinically diagnosed superficial basal cell carcinoma is associated with early infiltration by CD4 T cells and dendritic cells.

Barnetson RS, Satchell A, Zhuang L, Slade HB, Halliday GM.

Department of Dermatology, Melanoma and Skin Cancer Research Institute, University of Sydney at Royal Prince Alfred Hospital, Camperdown, Australia. ross canc.rpa.cs.nsw.gov.au

Imiquimod is presumed to clear basal cell carcinoma (BCC) through apoptosis mediated by cytokines and lymphocytes, with erosion often observed correlating with complete clearance. The objective was to determine the cellular immune response early in the course of treatment in order to examine whether cell mediated immunity could be responsible for imiquimod mediated regression of BCC. Sixteen adults with clinically diagnosed BCC were openly assigned to 5 days per week of drug (1, 2 or 4 weeks) or placebo (2 weeks) in groups of four. No baseline biopsy was performed. Post-treatment excision specimens were examined by routine and immunohistochemical staining. Treatment was associated with the early appearance of CD4 cells, activated dendritic cells and macrophages, with later infiltration by CD8 T cells. Dendritic cells continually increased with time, while macrophages reached a maximum at 1 week and then declined slightly. There were comparatively few neutrophils or gammadelta T cells. Early infiltrates were most prominent in the tumour and upper dermis. The results are consistent with a cell mediated immune response being responsible for the clearance of the BCC. Several immune-mediated tumour destruction mechanisms are likely to be involved.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15550144&dopt=Abstract imiquimod Aldara



Aldara
Bowenoid papulosis in a patient with AIDS treated with imiquimod: case report.

Nunes Mde G, Trope BM, Cavalcanti SM, Oliveira Ldo H, Mramos-E-Silva M.

Sector of Dermatology, HUCFF-UFRJ and School of Medicine, Rua Sorocaba 464/205 22271-110 Rio de Janeiro, Brasil.

A 53-year-old male patient with acquired immunodeficiency syndrome (AIDS) was treated with topical immunomodulator imiquimod for bowenoid papular. Clinically the lesions presented as condilomatous and papulous changes with color varying from skin color to grayish. The lesions were located in the glans and in the dorsum of the penis. Clinical diagnosis was confirmed by histopathological examination, and the polymerase chain reaction (PCR) demonstrated the presence of human papilloma virus (HPV) 16. It was decided to apply a topical treatment with imiquimod 5% cream three times a week for 16 weeks. Almost complete regression was obtained; the residual lesions were treated with a combined chemical cauterization by using 50% trichloroacetic acid followed by 25% podophylin. Although it is not a definitive treatment, the use of topical immunomodulator is one more therapeutic option in the selected HPV cases.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15588562&dopt=Abstract imiquimod Aldara



Aldara
A case of Bowenoid papulosis of the penis successfully treated with topical imiquimod cream 5%.

Goorney BP, Polori R.

Department of Genito-Urinary Medicine, Hope Hospital, Stott Lane, Manchester M6 8HD, UK. benjamin.goorney srht.nhs.uk

Bowenoid papulosis is a pre-malignant condition affecting the ano-genital area. Pathogenesis may be associated with high-risk human papillomavirus genotypes, and sexual transmission is the most likely mode of acquisition. Risk of progression to invasive disease is low. Treatment usually involves locally destructive or ablative therapies. We report well-tolerated, successful clearance of bowenoid papulosis of the penis in a 25-year-old male, using topical Aldara (imiquimod) cream 5%, once every other day for two months.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15601490&dopt=Abstract imiquimod Aldara



Aldara
Gene expression in actinic keratoses: pharmacological modulation by imiquimod.

Lysa B, Tartler U, Wolf R, Arenberger P, Benninghoff B, Ruzicka T, Hengge UR, Walz M.

Department of Dermatology, Heinrich-Heine University, Moorenstrasse 5, D-40225 Dusseldorf, Germany.

BACKGROUND: Actinic keratoses (AKs) are premalignant lesions that can progress into squamous cell carcinoma. Imiquimod, which belongs to the new class of immune-response modifiers, was recently shown to be effective in the treatment of AKs. The underlying mechanisms are not fully understood. OBJECTIVES: To study the expression of individual genes in uninvolved skin and AKs before therapy and to elucidate the way in which the expression of these genes is influenced by imiquimod therapy. METHODS: We treated 13 patients with AK with imiquimod and compared gene expression before, during (five patients) and after (eight patients) therapy with that in uninvolved skin. We analysed genes coding for inflammatory cytokines or their receptors, adhesion molecules, anti-apoptotic proteins, p53 and toll-like receptors (TLRs) by reverse-transcriptase polymerase chain reaction. RESULTS: Comparing uninvolved skin and untreated AK, we found significant differences in the expression of interleukin (IL)-6, hurpin, TLR7 and TLR8. During imiquimod therapy, we detected a further upregulation of interferon-alpha, IL-6, IL-10 receptor 1 and TLR7. In contrast, two anti-apoptotic genes, hurpin and HAX-1, were downregulated. We did not detect significant differences in gene expression for p53, tumour necrosis factor-alpha and alpha- and beta-catenins. Clinically, the upregulated expression of the proinflammatory cytokines correlated with the local inflammation induced by imiquimod. CONCLUSIONS: Our results indicate that specific differences in gene expression are detectable between AK and uninvolved skin. Imiquimod influenced the expression of most genes analysed in this study. This work extends previous findings on the effects of imiquimod on gene regulation in AKs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15606509&dopt=Abstract imiquimod Aldara