Xenobiotic acceleration of idiopathic systemic autoimmunity in lupus-prone bxsb mice.
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.
Pollard
K M
KM
W.M. Keck Autoimmune Disease Center, Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92337, USA. mpollard@scripps.edu
Pearson
D L
DL
Hultman
P
P
Deane
T N
TN
Lindh
U
U
Kono
D H
DH
D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D002843:Chromatin / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D008297:Male; D008628:Mercury / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D015262:Xenobiotics / Q000009:adverse effects*
D001323:Autoantibodies; D002843:Chromatin; D015262:Xenobiotics; D008628:Mercury