Biocompatibility of solid-dosage forms of anti-human immunodeficiency virus type 1 microbicides with the human cervicovaginal mucosa modeled ex vivo.

Trifonova, R.T., Pasicznyk, J.M., Fichorova, R.N.
Journal   Antimicrobial Agents and Chemotherapy.
Species  
Analytes Measured   IL-6 , IL-8 , IP-10
Matrix Tested   Serum
Year   2006
Volume   50
Page Numbers   4005-10
Application   Cytokines and Chemokines
Abstract
Topical anti-human immunodeficiency virus (HIV) microbicides are being sought to reduce the spread of HIV type 1 (HIV-1) during sexual intercourse. The success of this strategy depends upon the selection of formulations compatible with the natural vaginal mucosal barrier. This study applied ex vivo-modeled human cervicovaginal epithelium to evaluate experimental solid-dosage forms of the anti-HIV-1 microbicide cellulose acetate 1,2-benzenedicarboxylate (CAP) and over-the-counter (OTC) vaginal products for their impact on inflammatory mediators regarded as potential HIV-1-enhancing risk factors. We assessed product-induced imbalances between interleukin-1alpha (IL-1alpha) and IL-1beta and the natural IL-1 receptor antagonist (IL-1RA) and changes in levels of IL-6, tumor necrosis factor alpha, IL-8, gamma interferon inducible protein 10 (IP-10), and macrophage inflammatory protein 3alpha (MIP-3alpha), known to recruit and activate monocytes, dendritic cells, and T cells to the inflamed mucosa. CAP film and gel formulation, similarly to the hydroxyethylcellulose universal vaginal placebo gel and the OTC K-Y moisturizing gel, were nontoxic and caused no significant changes in any inflammatory biomarker. In contrast, OTC vaginal cleansing and contraceptive films containing octoxynol-9 or nonoxynol-9 (N-9) demonstrated similar levels of toxicity but distinct immunoinflammatory profiles. IL-1alpha, IL-1beta, IL-8, and IP-10 were increased after treatment with both OTC vaginal cleansing and contraceptive films; however, MIP-3alpha was significantly elevated by the N-9-based film only (P < 0.01). Although both films increased extracellular IL-1RA, the cleansing film only significantly elevated the IL-1RA/IL-1 ratio (P < 0.001). The N-9-based film decreased intracellular IL-1RA (P < 0.05), which has anti-inflammatory intracrine functions. This study identifies immunoinflammatory biomarkers that can discriminate between formulations better than toxicity assays and should be clinically validated in relevance to the risk of HIV-1 acquisition.

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Multiplex
V-PLEX Neuroinflammation Panel 1 Human Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Plus Neuroinflammation Panel 1 Human Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Chemokine Panel 1 NHP Kit
Eotaxin-3, IL-8, IL-8 (HA), IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Non-human primate
Multiplex
V-PLEX NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX NHP IL-6 Kit
IL-6 | Non-human primate
Singleplex
V-PLEX NHP IL-8 Kit
IL-8 | Non-human primate
Singleplex
V-PLEX NHP IP-10 Kit
IP-10 | Non-human primate
Singleplex
V-PLEX Plus Chemokine Panel 1 NHP Kit
Eotaxin-3, IL-8, IL-8 (HA), IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Non-human primate
Multiplex
V-PLEX Plus NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX Plus NHP IL-6 Kit
IL-6 | Non-human primate
Singleplex
V-PLEX Plus NHP IL-8 Kit
IL-8 | Non-human primate
Singleplex
V-PLEX Plus NHP IP-10 Kit
IP-10 | Non-human primate
Singleplex
V-PLEX Plus Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
Human IL-6 Antibody Bulk Product
IL-6
Human IL-8 Antibody Bulk Product
IL-8
Human IP-10 Antibody
IP-10
Mouse IL-6 Antibody
IL-6
Rat IL-6 Antibody
IL-6
V-PLEX Chemokine Panel 1 Human Kit
Eotaxin, Eotaxin-3, IL-8, IL-8 (HA), IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Human
Multiplex
V-PLEX Human Cytokine 30-Plex Kit
Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Human IL-6 Kit
IL-6 | Human
Singleplex
V-PLEX Human IL-8 Kit
IL-8 | Human
Singleplex
V-PLEX Human IP-10 Kit
IP-10 | Human
Singleplex
V-PLEX Human Proinflammatory Panel I (4-Plex)
IFN-γ, IL-1β, IL-6, TNF-α | Human
Multiplex
V-PLEX Human Proinflammatory Panel II (4-Plex)
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
V-PLEX Mouse IL-6 Kit
IL-6 | Mouse
Singleplex
V-PLEX Plus Chemokine Panel 1 Human Kit
Eotaxin, Eotaxin-3, IL-8, IL-8 (HA), IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Human
Multiplex
V-PLEX Plus Human Cytokine 30-Plex Kit
Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Plus Human IL-6 Kit
IL-6 | Human
Singleplex
V-PLEX Plus Human IL-8 Kit
IL-8 | Human
Singleplex
V-PLEX Plus Human IP-10 Kit
IP-10 | Human
Singleplex
V-PLEX Plus Human Proinflam. Panel I (4-Plex)
IFN-γ, IL-1β, IL-6, TNF-α | Human
Multiplex
V-PLEX Plus Human Proinflam. Panel II (4-Plex)
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
V-PLEX Plus Mouse IL-6 Kit
IL-6 | Mouse
Singleplex
V-PLEX Plus Proinflammatory Panel 1 Human Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α |