interleukin-8 and monolaurin

Staphylococcal menstrual toxic shock syndrome depends on vaginal production of exotoxins. Glycerol monolaurate (GML) inhibits Staphylococcus aureus exotoxin production in vitro. The purpose of this study was to determine whether GML, as a tampon fiber finish, inhibits production of exotoxins and the cytokine interleukin 8 (IL-8) during normal tampon use.. On day 2 of menstruation, when vaginal S. aureus counts are high in colonized women, study participants exchanged their own preferred tampons, after wearing them for 2-6 h, for study tampons with or without GML (assigned randomly and blindly), which they then wore for 4-6 h. The women's own tampons and the study tampons with or without GML were assayed for S. aureus, the exotoxins toxic shock syndrome toxin 1 and alpha-toxin, and IL-8.. A total of 225 women completed the study. S. aureus was present in the tampons of 41 women (18%). Lower numbers of S. aureus and the exotoxins were detected in study tampons with or without GML than in women's own tampons; lower amounts of the exotoxins were present in study tampons with GML than study tampons without GML. The IL-8 level was lower in tampons from women without vaginal S. aureus compared with women with S. aureus and was lower in study tampons with GML than in study tampons without GML.. Tampons that contain GML reduce S. aureus exotoxin production. S. aureus increases vaginal IL-8 levels, and GML reduces production of this proinflammatory cytokine. These results suggest that GML added to tampons provides additional safety relative to menstrual toxic shock syndrome as well as benefits for vaginal health generally, thus supporting the addition of GML to tampons.

Topics: Adolescent; Adult; Bacterial Toxins; Cariostatic Agents; Enterotoxins; Female; Humans; Interleukin-8; Laurates; Menstrual Hygiene Products; Monoglycerides; Staphylococcal Infections; Staphylococcus aureus; Superantigens; Vagina; Young Adult

Topics: Adenocarcinoma; Animals; Anti-Bacterial Agents; Cell Line, Tumor; Citrus paradisi; Gene Expression Regulation; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Lactobacillus plantarum; Laurates; Male; Mice; Mice, Inbred BALB C; Monoglycerides; Plant Extracts; Probiotics; Specific Pathogen-Free Organisms; Stomach; Stomach Neoplasms

The use of microbicides is a promising approach for the prevention of HIV-1 transmission. Unfortunately, various candidates failed in clinical trials. In some cases, the candidate microbicide even resulted in enhanced virus transmission. Therefore, there is an urgent need to develop more predictive preclinical strategies to anticipate the in vivo efficiency/toxicity rate, including in vitro assays that evaluate effects on epithelial integrity and inflammation. The present study aims to identify potential safety issues concerning the use of microbicides and excipients commonly used in vaginal microbicide preparations. The toxicities of various active pharmaceutical ingredients (APIs; TMC-120, UC-781, tenofovir [PMPA], PRO-2000, and glycerol monolaurate [GML]) and excipients (preservatives, cosolvents, surfactants, and cyclodextrins) were evaluated using an in vitro dual-chamber model and uterine cervical explants. Epithelial viability and permeation of fluorescent virus-sized beads, as well as induction of interleukin-8 (IL-8; as a sensitive marker of an inflammatory response), were assessed. Surprisingly, cell viability and epithelial layer integrity were compromised by most excipients at concentrations near the typical concentration used in vaginal gels, and a significant increase in the production of IL-8 was observed at subtoxic concentrations. Within the APIs, TMC-120, UC-781, and PMPA showed higher selectivity indices than PRO-2000 and GML. In conclusion, identification of safety issues concerning the use of pharmaceutical excipients could help to formulate less toxic vaginal microbicide preparations.

Topics: Adenine; Anilides; Anti-Infective Agents; Benzofurans; Cell Line; Cell Survival; Cervix Uteri; Epithelium; Female; Furans; HIV Infections; Humans; In Vitro Techniques; Interleukin-8; Laurates; Monoglycerides; Naphthalenesulfonates; Organophosphonates; Polymers; Reverse Transcriptase Inhibitors; Tenofovir; Thioamides

Although there has been great progress in treating human immunodeficiency virus 1 (HIV-1) infection, preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission. Nonetheless, studies of vaginal transmission in the simian immunodeficiency virus (SIV)-rhesus macaque (Macacca mulatta) model point to opportunities at the earliest stages of infection in which a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry. Here we show in this SIV-macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3alpha (also known as CCL20), plasmacytoid dendritic cells and CCR5(+ )cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruits CD4(+) T cells to fuel this obligate expansion. We then show that glycerol monolaurate-a widely used antimicrobial compound with inhibitory activity against the production of MIP-3alpha and other proinflammatory cytokines-can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo it can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This new approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for the development of effective interventions to block HIV-1 mucosal transmission.

Topics: Acute Disease; Animals; Body Fluids; CD4-Positive T-Lymphocytes; Cell Cycle Proteins; Cervix Uteri; Chemokine CCL20; Dendritic Cells; Female; Gene Expression Profiling; GPI-Linked Proteins; HIV-1; Interleukin-8; Laurates; Macaca mulatta; Membrane Proteins; Monoglycerides; Mucous Membrane; Receptors, CCR5; RNA, Viral; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Time Factors; Vagina

Topics: Adolescent; Adult; Bacterial Toxins; Cariostatic Agents; Enterotoxins; Female; Humans; Interleukin-8; Laurates; Menstrual Hygiene Products; Monoglycerides; Staphylococcus aureus; Superantigens; Vagina; Young Adult