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K. Michael Pollard,¹ Deborah L. Pearson,¹ Per Hultman,² Tricia N. Deane,¹ Ulf Lindh,³ and Dwight H. Kono⁴

¹W.M. Keck Autoimmune Disease Center, Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California, USA
²Division of Molecular and Immunological Pathology, Department of Health and Environment, Linköping University, Linköping, Sweden
³Center for Metal Biology, Uppsala, Sweden
⁴Department of Immunology, Scripps Research Institute, La Jolla, California, USA

Abstract

The diverse genetic backgrounds of lupus-prone murine models, which produce both quantitative and qualitative differences in disease expression, may be a valuable resource for studying the influence of environmental exposure on autoimmune disease in sensitive populations. We tested this premise by exposing autoimmune-prone BXSB and the nonautoimmune C57BL/6 mice to the heavy metal mercury. Although both strains express a nonsusceptible H-2 haplotype, exposure to mercury accelerated systemic autoimmunity in both male and female BXSB mice, whereas the C57BL/6 mice were resistant. The subclasses of antichromatin antibodies elicited in BXSB mice by mercury exposure were more consistent with the predominant Th1-type response of idiopathic disease than with the Th2-type response found in mercury-induced autoimmunity (HgIA) . The appearance and magnitude of both humoral and cellular features of systemic autoimmunity correlated with the mercury dose. Furthermore, environmentally relevant tissue levels of mercury were associated with exacerbated systemic autoimmunity. These studies demonstrate that xenobiotic exposure can accelerate spontaneous systemic autoimmunity, and they support the possibility that low-level xenobiotic exposure enhances susceptibility to systemic autoimmunity in genetically susceptible individuals. Key words: autoantibodies, autoimmunity, in vivo animal models, lupus, rodent. Environ Health Perspect 109:27-33 (2001) . [Online 30 November 2000]

http://ehpnet1.niehs.nih.gov/docs/2001/109p27-33pollard/ abstract.html

Address correspondence to K.M. Pollard, Department of Molecular and Experimental Medicine, MEM131, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 USA. Telephone: (858) 784-9214. Fax: (858) 784-2131. E-mail: mpollard@scripps.edu

We thank Miyo S. Park for technical assistance.

This publication was made possible by grants ES09802, ES07511, ES08666, and ES08080 from the National Institute of Environmental Health Sciences, NIH, and Swedish Medical Research Council Grant 09453. This is publication number 11775 MEM from The Scripps Research Institute, La Jolla, California.

Received 13 June 2000 ; accepted 22 August 2000.