Enhancement of the innate and cellular immune response in patients with genital warts treated with topical imiquimod cream 5

• Published in: Antiviral research 1999-08, Vol.43 (1), p.55-63
• Main Authors: Arany, Istvan, Tyring, Stephen K, Stanley, Margaret A, Tomai, Mark A, Miller, Richard L, Smith, Michael H, McDermott, Daniel J, Slade, Herbert B
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; AIDS/HIV; Aldara; Aminoquinolines - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antigens, CD - genetics; Antigens, CD - metabolism; Antiviral agents; Biological and medical sciences; Cell Differentiation; Cell Division; Condylomata acuminata; Condylomata Acuminata - drug therapy; Condylomata Acuminata - immunology; Condylomata Acuminata - virology; Cytokine; Cytokines - genetics; Cytokines - metabolism; Double-Blind Method; Female; Genital Diseases, Female - drug therapy; Genital Diseases, Female - immunology; Genital Diseases, Female - virology; Genital Diseases, Male - drug therapy; Genital Diseases, Male - immunology; Genital Diseases, Male - virology; Human papilloma virus; Humans; Imiquimod; Interferon; Interferon Inducers - therapeutic use; Keratinocytes - pathology; Male; Medical sciences; Middle Aged; Papillomaviridae - genetics; Papillomaviridae - isolation & purification; Papillomaviridae - physiology; Pharmacology. Drug treatments; Polymerase Chain Reaction; RNA, Messenger - metabolism; Viral Load
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/S0166-3542(99)00033-9

The mechanism of action of imiquimod 5% cream applied topically to patients with genital warts was evaluated in a double-blind, placebo-controlled study. Imiquimod (16 patients) or placebo (three patients) was applied three times per week for up to 16 weeks. All imiquimod-treated patients had a ≥75% reduction in total wart area while only one of three placebo-treated patients had a similar reduction. Wart biopsies were taken at prestudy, week 6, and end of treatment. Polymerase chain reaction (PCR) for human papillomavirus (HPV) DNA and reverse transcriptase (RT)-PCR for messenger (m)RNAs were used to identify cytokines, cellular markers, viral gene products, and cell cycle markers in these biopsies. Treatment with imiquimod, an immune response modifier, stimulated significant increases in mRNA for interferon (IFN)-α, IFN-γ and 2′,5′ oligoadenylate synthetase (2′,5′-AS) as well as a tendency towards increases in tumor necrosis factor (TNF)-α and interleukin-12 p40. Significant increases in mRNA for CD4 and a trend toward increases in CD8 were also observed in imiquimod-treated patients, suggesting activation of a cell mediated immune response. Imiquimod administration was also associated with a significant decrease in viral load as measured by HPV DNA and L1 mRNA. The effects on HPV markers were accompanied by an apparent decrease in mRNA expression for markers of cell proliferation and an increase in mRNA for markers of keratinocyte differentiation and tumor suppressors.