title: Immune stimulation following dermal exposure to unsintered indium tin oxide.
abstract: In recent years, several types of pulmonary pathology, including alveolar proteinosis, fibrosis, and emphysema, have been reported in workers in the indium industry. To date, there remains no clear understanding of the underlying mechanism(s). Pulmonary toxicity studies in rats and mice have demonstrated the development of mediastinal lymph node hyperplasia and granulomas of mediastinal lymph nodes and bronchus-associated lymphoid tissues following exposure to indium tin oxide. Given the association between exposure to other metals and the development of immune-mediated diseases, these studies were undertaken to begin to investigate the immuno-modulatory potential of unsintered indium tin oxide (uITO) in a mouse model. Using modifications of the local lymph node assay, BALB/c mice (five animals/group) were exposed topically via intact or breached skin or injected intradermally at the base of the ear pinnae with either vehicle or increasing concentrations 2.5-10% uITO (90:10 indium oxide/tin oxide, particle size <50 nm). Dose-responsive increases in lymphocyte proliferation were observed with a calculated EC3 of 4.7% for the intact skin study. Phenotypic analysis of draining lymph node cells following intradermal injection with 5% uITO yielded a profile consistent with a T-cell-mediated response. These studies demonstrate the potential for uITO to induce sensitization and using lymphocyte proliferation as a biomarker of exposure, and demonstrate the potential for uITO to penetrate both intact and breached skin.
authors.affiliation: Case Western University, ARC Veterinary Services , Cleveland, OH , USA and.
authors.forename: Kristie
authors.initials: K
authors.lastname: Brock
authors.forename: Stacey E
authors.initials: SE
authors.lastname: Anderson
authors.forename: Ewa
authors.initials: E
authors.lastname: Lukomska
authors.forename: Carrie
authors.initials: C
authors.lastname: Long
authors.forename: Katie
authors.initials: K
authors.lastname: Anderson
authors.forename: Nikki
authors.initials: N
authors.lastname: Marshall
authors.forename: B Jean
authors.initials: BJ
authors.lastname: Meade
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020405:Dermis / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005355:Fibrosis; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007114:Immunization; D007204:Indium / Q000633:toxicity*; D007221:Industry; D008168:Lung / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D016273:Occupational Exposure / Q000009:adverse effects; D011649:Pulmonary Alveolar Proteinosis / Q000139:chemically induced / Q000276:immunology*; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D017971:Tin Compounds / Q000633:toxicity*
chemical_list: D017971:Tin Compounds; D007204:Indium; C045358:stannic oxide
keywords: Immune stimulation; immunotoxicity; unsintered indium tin oxide