[Mechanisms of imiquimod indirect antiviral activity].
The potential role of an immune response in HPV-related anogenital disorders had already been anticipated by clinicians. Indeed the lesions efflorescence and the relapsing HPV infection in HIV positive patients as well as the lack of recurrence in patients with spontaneous cure, provided relevant clues for a likely immune mechanism. At present time, the role of the immune system in the development of HPV-related anogenital disorders is well established : HPV induce a humoral and cell mediated immune response. This response is mainly exerted towards infected cells; it is also exerted at the systemic level, through antibodies synthesis, but this pathway remains a secondary one. Due to the limits of the present therapies (either purely destructive and characterized by the rate of recurrences, or antiviral, but difficult to use), it was necessary to find a new treatment type which enhances the local immune response, results in the disappearance of lesions and allows for a decrease in the risk of recurrences. The original mechanism of action of the first cell-mediated immune response modifier: imiquimod, for local use (Aldara 5 % cream) is an answer to this need. The first positive results observed in vitro and in animals were confirmed in patients with HPV anogenital warts in a double blind placebo-controlled study: imiquimod inhibits HPV replication and results in the condyloma regression. Its action is based on the combined activation of the natural local immunity, by stimulating interferon alpha; and of the acquired immunity, by stimulating a T-cell mediated immune response. Thus imiquimod appears to be an original antiviral compound, because it does not act directly on the virus itself.
Hober
D
D
Service de virologie, Upres EA3610 CHRU, Lille, France. dhober@chru-lille.fr
Ajram
L
L
Chehadeh
W
W
Lazrek
M
M
Goffard
A
A
Dewilde
A
A
Wattré
P
P
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000328:Adult; D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D001004:Anus Diseases / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery; D003218:Condylomata Acuminata / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D005831:Genital Diseases, Female / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery; D005832:Genital Diseases, Male / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery; D006679:HIV Seropositivity; D000882:Haplorhini; D006801:Humans; D000077271:Imiquimod; D007111:Immunity, Cellular; D007369:Interferon Inducers / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009824:Ointments; D027383:Papillomaviridae / Q000187:drug effects* / Q000276:immunology; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D012008:Recurrence; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000914:Antibodies, Viral; D000998:Antiviral Agents; D007369:Interferon Inducers; D009824:Ointments; D010919:Placebos; D000077271:Imiquimod