Xenobiotic acceleration of idiopathic systemic autoimmunity in lupus-proneBXSB mice

The diverse genetic backgrounds of lupus-prone murine models, which produce both quantitative and qualitative differences in disease expression, may b e a valuable resource for studying the influence of environmental exposure on autoimmune disease in sensitive populations. We tested this premise by e xposing autoimmune-prone BXSB and the nonautoimmune C57BL/6 mice to the hea vy metal mercury. Although both strains express a nonsusceptible H-2 haplot ype, 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 diseas e than with the Th2-type response found in mercury-induced autoimmunity (Hg IA). The appearance and magnitude of both humoral and cellular features of systemic autoimmunity correlated with the mercury dose. Furthermore, enviro nmentally relevant tissue levels of mercury were associated with exacerbate d systemic autoimmunity. These studies demonstrate that xenobiotic exposure can accelerate spontaneous systemic autoimmunity, and they support the pos sibility that low-level xenobiotic exposure enhances susceptibility to syst emic autoimmunity in genetically susceptible individuals.