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Effects of Libby amphibole asbestos exposure on two rat models of rheumatoid arthritis
Citation:
SALAZAR, K. D., C. B. COPELAND, AND R. W. LUEBKE. Effects of Libby amphibole asbestos exposure on two rat models of rheumatoid arthritis. Presented at Society of Toxicology(SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
Our goal was to determine whether exposure to Libby amphibole (LA) modulates the disease course of RA
Description:
Epidemiological data suggests 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). Our goal was to determine whether exposure to Libby amphibole (LA) modulates the disease course of RA. We utilized the collagen-induced arthritis (CIA) and the Streptococcal cell wall (SCW) models of RA. The SCW arthritis model induces a local inflammatory reaction in one hind ankle that mimics the physiological milieu associated with RA in humans. The CIA model is a systemic model that produces paw inflammation in all 4 limbs and autoantibodies similar to human patients with RA. To determine if LA affects onset and progression of RA, female Lewis rats were equally divided into 6 asbestos dose groups and 1 vehicle control group. Rats were intratracheally instilled biweekly for 13-weeks with total doses of 0.15, 0.5, 1.5, 5.0 mg LA or 0.5 or 1.5 mg amosite asbestos (positive control). Following the final instillation, joint inflammation was induced with either the SCW or CIA model. Swelling was quantified with a digital caliper and serum was analyzed for autoantibodies via ELISA and indirect immunofluorescence. Preliminary results from 2 experiments suggest that amosite, but not LA, exposure enhanced the magnitude of ankle swelling in the SCW model. However, neither LA nor amosite exposure affects the kinetics of the join inflammation in the CIA model. Both amosite and LA exposure increased the number of rats with circulating anti-nuclear antibodies (ANA). The majority of ANA-positive animals presented a similar ANA staining pattern which indicates the upregulation of autoantibodies with similar specificity. Future studies will identify the specificity of the upregulated ANA and characterize the effect of amphibole exposure on RAassociated antibodies. This abstract does not reflect EPA policy.