Enhancement of the innate and cellular immune response in patients with genital warts treated with topical imiquimod cream 5%.
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 > or =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)-alpha, IFN-gamma and 2',5' oligoadenylate synthetase (2',5'-AS) as well as a tendency towards increases in tumor necrosis factor (TNF)-alpha 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.
Arany
I
I
Department of Microbiology and Immunology, The University of Texas Medical Branch at Galveston, 77555-1019, USA.
Tyring
S K
SK
Stanley
M A
MA
Tomai
M A
MA
Miller
R L
RL
Smith
M H
MH
McDermott
D J
DJ
Slade
H B
HB
D000293:Adolescent; D000328:Adult; D000634:Aminoquinolines / Q000627:therapeutic use*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D003218:Condylomata Acuminata / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005831:Genital Diseases, Female / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D005832:Genital Diseases, Male / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D000077271:Imiquimod; D007369:Interferon Inducers / Q000627:therapeutic use*; D015603:Keratinocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D019562:Viral Load
D000634:Aminoquinolines; D015703:Antigens, CD; D016207:Cytokines; D007369:Interferon Inducers; D012333:RNA, Messenger; D000077271:Imiquimod