Cytokine induction and modifying the immune response to human papilloma virus with imiquimod.
Imiquimod is the newest in a class of drugs known as immune response modifiers. In preclinical studies, imiquimod induced the production of cytokines - the principal cytokine for antiviral activity being interferon alpha. Imiquimod does not inhibit viruses directly, nor does it cause direct, non-specific cytolytic destruction [1]. Preclinical studies suggest that its antiviral action results from in vivo cytokine-induced activation of the immune system. This paper reviews a recent double blind, placebo-controlled study designed to evaluate this hypothesis. The results of this study showed that wart regression following treatment with imiquimod strongly correlated with a decrease in viral DNA and gene transcripts; a decrease in mRNA expression for proteins associated with cellular proliferation, and an increase in keratinocyte markers. These results support the hypothesis that stimulation of local cytokines by imiquimod leads to a reduction in human papilloma virus (HPV) load; to wart regression and to the normalisation of keratinocyte proliferation without evidence of scarring.
Slade
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3M Pharmaceuticals, Building 270-3A-01, 3M Center, St Paul, Minnesota, USA. hbslade@mmm.com
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000634:Aminoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D003218:Condylomata Acuminata / Q000188:drug therapy / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D004279:DNA, Viral / Q000032:analysis / Q000187:drug effects; D006801:Humans; D000077271:Imiquimod; D007369:Interferon Inducers / Q000494:pharmacology / Q000627:therapeutic use*; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology*; D030361:Papillomavirus Infections / Q000188:drug therapy* / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D014412:Tumor Virus Infections / Q000188:drug therapy* / Q000276:immunology
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D016207:Cytokines; D004279:DNA, Viral; D007369:Interferon Inducers; D000077271:Imiquimod