title: Effects of Libby amphibole asbestos exposure on two models of arthritis in the Lewis rat.
abstract: Epidemiological data suggest that occupational exposure to the amphibole-containing vermiculite in Libby, MT, was associated with increased risk for developing autoimmune diseases and had an odds ratio of 3.23 for developing rheumatoid arthritis (RA). The collagen-induced arthritis (CIA) and the peptidoglycan-polysaccharide (PG-PS) models of RA were employed to determine whether exposure to Libby amphibole (LA) induced a more rapid onset, increased expression, or prolonged course of RA. Female Lewis rats were intratracheally instilled with total doses of 0.15, 0.5, 1.5, or 5 mg LA or 0.5 or 1.5 mg amosite asbestos, and arthritis was induced with either the PG-PS or CIA model. Neither LA nor amosite exposure affected the disease course in the CIA model, or the production of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibodies. LA exposure reduced swelling in the PG-PS model and decreased anti-PG-PS and total immunoglobulin M (IgM) antibody titers. Both amosite and LA exposure increased the number of rats with circulating anti-nuclear antibodies (ANA), the majority of which presented a speckled staining pattern. However, this ANA enhancement was not dose responsive. These results failed to show a positive correlation between LA exposure and RA disease in two animal models, although upregulated ANA suggest an altered immunological profile consistent with other systemic autoimmune diseases.
authors.affiliation: Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Salazar
authors.forename: Carey B
authors.initials: CB
authors.lastname: Copeland
authors.forename: Robert W
authors.initials: RW
authors.lastname: Luebke
mesh_terms: D000538:Aluminum Silicates / Q000737:chemistry; D000818:Animals; D000906:Antibodies / Q000097:blood; D001169:Arthritis, Experimental / Q000139:chemically induced*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced*; D017636:Asbestos, Amphibole / Q000008:administration & dosage / Q000633:toxicity*; D015415:Biomarkers; D004305:Dose-Response Relationship, Drug; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007278:Injections, Spinal; D007596:Joints / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors
chemical_list: D000538:Aluminum Silicates; D000906:Antibodies; D017636:Asbestos, Amphibole; D015415:Biomarkers; D007074:Immunoglobulin G; C003760:vermiculite