Aldara
Plasmacytoid dendritic cells produce cytokines and mature in response to the TLR7 agonists, imiquimod and resiquimod.

Gibson SJ, Lindh JM, Riter TR, Gleason RM, Rogers LM, Fuller AE, Oesterich JL, Gorden KB, Qiu X, McKane SW, Noelle RJ, Miller RL, Kedl RM, Fitzgerald-Bocarsly P, Tomai MA, Vasilakos JP.

Department of Pharmacology, 3M Pharmaceuticals, 3M Center, 270-2S-06, St. Paul, MN 55144-1000, USA.

The immune response modifiers, imiquimod and resiquimod, are TLR7 agonists that induce type I interferon in numerous species, including humans. Recently, it was shown that plasmacytoid dendritic cells (pDC) are the primary interferon-producing cells in the blood in response to viral infections. Here, we characterize the activation of human pDC with the TLR7 agonists imiquimod and resiquimod. Results indicate that imiquimod and resiquimod induce IFN-alpha and IFN-omega from purified pDC, and pDC are the principle IFN-producing cells in the blood. Resiquimod-stimulated pDC also produce a number of other cytokines including TNF-alpha and IP-10. Resiquimod enhances co-stimulatory marker expression, CCR7 expression, and pDC viability. Resiquimod was compared throughout the study to the pDC survival factors, IL-3 and IFN-alpha; resiquimod more effectively matures pDC than either IL-3 or IFN-alpha alone. These results demonstrate that imidazoquinoline molecules directly induce pDC maturation as determined by cytokine induction, CCR7 and co-stimulatory marker expression and prolonging viability.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12470615&dopt=Abstract imiquimod Aldara



Aldara
The imidazoquinolines, imiquimod and R-848, induce functional, but not phenotypic, maturation of human epidermal Langerhans' cells.

Burns RP Jr, Ferbel B, Tomai M, Miller R, Gaspari AA.

Department of Dermatology, 3M Pharmaceuticals, St. Paul, Minnesota, USA.

Imiquimod (R-837) and its more potent derivative (R-848) are imidazoquinolines that have adjuvant activity in cultured human mononuclear cells. Its mechanism of action on epidermal antigen-presenting cells is not known. The purpose of the present investigation was to determine whether imiquimod and R-848 affect human epidermal Langerhans' cells' (LC) in vitro maturation. Pulse incubations (6-16 h) of cultured unfractionated epidermal cells or highly enriched LC suspensions with either imiquimod or R-848 (0. 05-5.0 microg/ml of culture medium) reproducibly enhanced their ability to induce T-cell proliferation in a primary mixed lymphocyte reaction. There was a 30 to 300% increase in T-lymphocyte proliferation induced by either imiquimod- or R-848-treated LC when compared to control, untreated LC. IFN-gamma secretion by T-lymphocytes stimulated by imiquimod- or R-848-treated LC was increased compared to control, untreated LC. After a 6-h incubation, phenotypic analysis of control-, imiquimod-, or R-848-treated LC indicated that such antigen-presenting cells were in an "intermediate" state of maturation (CD1a(+), HLA-DR, DP, DQ(bright+), CD40(low+), CD86(high+), and CD80(low+)). RNase protection assays demonstrated that either imiquimod or R-848 treatments increased steady-state transcripts encoding for IL-12 p40, IL-1beta, TNF-alpha, and IL-1 receptor antagonist by LC. These data indicate that imiquimod and R-848 dissociate the functional maturation (cytokine-mediated) and phenotypic maturation of epidermal LC. These data warrant further exploration for the use of imidazoquinoline-treated LC or other DC subsets for processing and presentation of viral peptides to Th-lymphocytes as a novel vaccine strategy to induce protective antiviral responses. Copyright 2000 Academic Press.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10607486&dopt=Abstract imiquimod Aldara



Aldara
Is imiquimod effective and safe for actinic keratosis?

Walker JK, Koenig C.

Department of Family and Community Medicine, University of Missouri-Columbia, USA. WalkerJK health.missouri.edu

Imiquimod 5% cream, applied 3 times per week for 12 weeks, is effective for treatment of actinic keratosis. Severe erythema and other local reactions occurred in almost everyone receiving treatment, due to imiquimod's immune system-modulating effects. The 25 patients in the treatment group tolerated these adverse effects well. Despite these effects, imiquimod can be used as an alternative to traditional cryotherapy for the treatment of actinic keratosis among selected, motivated

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12620165&dopt=Abstract imiquimod Aldara



Aldara
[Imiquimod in the treatment of recalcitrant warts: a new therapy option?]

[Article in German]

Hesterberg U, Bohlen LM, Brand CU.

Dermatologische Universitatsklinik, Inselspital Bern.

Recalcitrants viral warts can pose a therapeutic challenge to the treating physician. In a clinical study, we documented the effect of imiquimod 5% cream (Aldara) on recalcitrants warts in 22 patients. A complete and partial clearing of the warts was achieved in 41% and 50%, respectively. In only 9% of patients no improvement could be observed. Beside the very often observed perilesional erythema, which correlated well with good treatment response, no relevant side effects were documented. Imiquimod 5% cream (Aldara) is an efficient, easy to perform ambulatory treatment modality for recalcitrants HPV induced warts with few side effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12693144&dopt=Abstract imiquimod Aldara



Aldara
The cost-effectiveness of patient-applied treatments for anogenital warts.

Williams P, von Krogh G.

PAREXEL MMS, Uxbridge, UK. paul.williams parexel.com

A model was developed to estimate the cost-effectiveness of podophyllotoxin and imiquimod for self-treatment of anogenital warts. The effectiveness endpoint was sustained clearance after treatment and a subsequent follow-up period of approximately 12 weeks. Effectiveness of podophyllotoxin was estimated from a quantitative summary of nine placebo-controlled trials, while effectiveness of imiquimod was based on a quantitative summary of six placebo-controlled trials. Costs were considered from a UK health service provider perspective; drug acquisition costs were obtained from the British National Formulary and health service costs of clinic attendance were based on a recent survey of GUM clinics. The impact of uncertainty was explored in a wide range of one-way and probabilistic (multi-way) sensitivity analyses. The cost per sustained clearance was 313 for podophyllotoxin and 606 for imiquimod. The modest and statistically insignificant incremental effectiveness of imiquimod was purchased at high cost-2476 per additional sustained clearance. Sensitivity analyses showed the economic superiority of podophyllotoxin to be robust and statistically very significant.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12716491&dopt=Abstract imiquimod Aldara