title: Nonsteroidal anti-inflammatory drugs do not interfere with imiquimod treatment for usual type vulvar intraepithelial neoplasia.
abstract: Imiquimod has been shown to be an effective treatment for usual type vulvar intraepithelial neoplasia (uVIN). Since local inflammation and burning are common side effects, patients often use nonsteroidal anti-inflammatory drugs (NSAIDs). Our study investigated whether NSAID-use, which has been documented to inhibit the cell-mediated immune response, interferes with the outcome of imiquimod treatment. Monocyte-derived dendritic cells (moDCs) and Langerhans cells (moLCs) were cultured in the presence of NSAIDs. The expression of relevant surface markers (CD80, CD86, CD40, HLA-DR, CCR6 and CCR7), stimulatory function, and cytokine production were evaluated. Furthermore, we analyzed in uVIN patients whether frequent NSAID-use had an effect on the clinical response and on immunocompetent cell counts before and after imiquimod treatment. Although an effect was observed on the expression of moDC and moLC maturation markers, NSAIDs did not affect the ability of moDCs and moLCs to stimulate allogeneic T-cell proliferation, or the production of cytokines in an allogeneic T-cell stimulation assay. In agreement with this, in uVIN patients treated with imiquimod, no interference of frequent NSAID-use with clinical outcome was observed. However, we did notice that high CD1a(+) and CD207(+) cell counts in frequent NSAID-users before treatment seemed to predict a favourable response to imiquimod treatment. Our data indicate that NSAID-use does not seem to interfere with moDC and moLC function and does not interfere with immunomodulatory properties of imiquimod in uVIN patients. Therefore, NSAIDs can safely be used to reduce imiquimod side effects in uVIN patients during treatment.
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, The Netherlands. a.terlou@erasmusmc.nl
authors.forename: Annelinde
authors.initials: A
authors.lastname: Terlou
authors.forename: Alex
authors.initials: A
authors.lastname: Kleinjan
authors.forename: Ilse
authors.initials: I
authors.lastname: Beckmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Heijmans-Antonissen
authors.forename: Manon
authors.initials: M
authors.lastname: van Seters
authors.forename: Lindy A M
authors.initials: LA
authors.lastname: Santegoets
authors.forename: Marc
authors.initials: M
authors.lastname: van Beurden
authors.forename: Theo J M
authors.initials: TJ
authors.lastname: Helmerhorst
authors.forename: Leen J
authors.initials: LJ
authors.lastname: Blok
mesh_terms: D000634:Aminoquinolines / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001706:Biopsy; D002278:Carcinoma in Situ / Q000188:drug therapy* / Q000276:immunology; D002469:Cell Separation; D004347:Drug Interactions; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D000077271:Imiquimod; D007150:Immunohistochemistry; D014846:Vulvar Neoplasms / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000634:Aminoquinolines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D000077271:Imiquimod