ABSTRACT
Triclosan is an antimicrobial chemical incorporated into many personal, medical and household products. Approximately, 75% of the U.S. population has detectable levels of triclosan in their urine, and although it is not typically considered a contact sensitizer, recent studies have begun to link triclosan exposure with augmented allergic disease. We examined the effects of dermal triclosan exposure on the skin and lymph nodes of mice and in a human skin model to identify mechanisms for augmenting allergic responses. Triclosan (0%-3%) was applied topically at 24-h intervals to the ear pinnae of OVA-sensitized BALB/c mice. Skin and draining lymph nodes were evaluated for cellular responses and cytokine expression over time. The effects of triclosan (0%-0.75%) on cytokine expression in a human skin tissue model were also examined. Exposure to triclosan increased the expression of TSLP, IL-1ß, and TNF-α in the skin with concomitant decreases in IL-25, IL-33, and IL-1α. Similar changes in TSLP, IL1B, and IL33 expression occurred in human skin. Topical application of triclosan also increased draining lymph node cellularity consisting of activated CD86(+)GL-7(+) B cells, CD80(+)CD86(+) dendritic cells, GATA-3(+)OX-40(+)IL-4(+)IL-13(+) Th2 cells and IL-17 A(+) CD4 T cells. In vivo antibody blockade of TSLP reduced skin irritation, IL-1ß expression, lymph node cellularity, and Th2 responses augmented by triclosan. Repeated dermal exposure to triclosan induces TSLP expression in skin tissue as a potential mechanism for augmenting allergic responses.
Subject(s)
Anti-Infective Agents, Local/toxicity , Cytokines/biosynthesis , Dermatitis, Allergic Contact/pathology , Stromal Cells/metabolism , Th2 Cells/drug effects , Th2 Cells/immunology , Triclosan/toxicity , Adaptive Immunity/drug effects , Administration, Topical , Animals , Dermatitis, Allergic Contact/immunology , Humans , In Vitro Techniques , Lymph Nodes/drug effects , Mice , Mice, Inbred BALB C , Stromal Cells/drug effects , Thymic Stromal LymphopoietinABSTRACT
BACKGROUND: Using non-powdered, low-protein natural rubber latex (NRL) gloves has been shown to reduce the elicitation of respiratory symptoms in latex-allergic individuals; however, the role of dermal exposure in the induction of sensitization is not completely understood. OBJECTIVE: These studies were conducted to (1) determine levels of NRL protein in gloves currently in use and (2) evaluate, using a murine model, the potential for dermal exposure to induce NRL sensitization and subsequent airway hyperreactivity upon respiratory challenge. METHODS: Total extractable protein and NRL allergen levels were evaluated from 38 glove samples using the Lowry and CAP inhibition assays, respectively. BALB/c mice were dermally exposed to non-ammoniated latex (NAL, 6.25-25 microg) 5 days/week for 13 weeks and monitored weekly/biweekly for IgE levels. Airway hyperreactivity was determined following respiratory challenge with methacholine (MCH) or NAL proteins on days 60 and 93, respectively. RESULTS: Glove total protein and NRL allergen levels ranged from below the limit of detection to 946 microg/g and from 0.002 to 112 microg/g, respectively. Mice demonstrated dose-dependent increases in total serum IgE levels by day 58 with increased airway hyperreactivity observed upon respiratory challenge with MCH (day 60) or NAL proteins (day 93). CONCLUSIONS: These studies investigated the continued use of gloves with high levels of total extractable protein and NRL allergen. The potential for dermal exposure to induce NRL-specific IgE and airway hyperreactivity upon respiratory challenge suggests there should be continued concern regarding the induction of sensitization in individuals using non-powdered latex gloves.