Havarinasab S, Lambertsson L, Qvarnström J, Hultman P
Molecular and Immunological Pathology (AIR), Department of Molecular and Clinical Medicine, Linköping University, SE-581 85 Linköping, Sweden.
Toxicol Appl Pharmacol. 2004 Jan 15;194(2):169-79. doi: 10.1016/j.taap.2003.09.006.
The organic compound ethylmercurithiosalicylate (thimerosal), which is primarily present in the tissues as ethylmercury, has caused illness and several deaths due to erroneous handling when used as a disinfectant or as a preservative in medical preparations. Lately, possible health effects of thimerosal in childhood vaccines have been much discussed. Thimerosal is a well-known sensitizing agent, although usually of no clinical relevance. In rare cases, thimerosal has caused systemic immune reactions including acrodynia. We have studied if thimerosal might induce the systemic autoimmune condition observed in genetically susceptible mice after exposure to inorganic mercury. A.SW mice were exposed to 1.25-40 mg thimerosal/l drinking water for 70 days. Antinucleolar antibodies, targeting the 34-kDa protein fibrillarin, developed in a dose-related pattern and first appeared after 10 days in the two highest dose groups. The lowest observed adverse effect level (LOAEL) for antifibrillarin antibodies was 2.5 mg thimerosal/l, corresponding to an absorbed dose of 147 microg Hg/kg bw and a concentration of 21 and 1.9 microg Hg/g in the kidney and lymph nodes, respectively. The same LOAEL was found for tissue immune-complex deposits. The total serum concentration of IgE, IgG1, and IgG2a showed a significant dose-related increase in thimerosal-treated mice, with a LOAEL of 5 mg thimerosal/l for IgG1 and IgE, and 20 mg thimerosal/l for IgG2a. The polyclonal B-cell activation showed a significant dose-response relationship with a LOAEL of 10 mg thimerosal/l. Therefore, thimerosal induces in genetically susceptible mice a systemic autoimmune syndrome very similar to that seen after treatment with inorganic mercury, although a higher absorbed dose of Hg is needed using thimerosal. The autoimmune syndrome induced by thimerosal is different from the weaker and more restricted autoimmune reaction observed after treatment with an equipotent dose of methylmercury.
有机化合物硫柳汞（乙基汞硫柳酸酯）在组织中主要以乙基汞的形式存在，在用作消毒剂或医疗制剂的防腐剂时，因处理不当已导致疾病和数起死亡事件。最近，硫柳汞对儿童疫苗可能产生的健康影响受到了广泛讨论。硫柳汞是一种知名的致敏剂，尽管通常无临床相关性。在罕见情况下，硫柳汞会引发包括肢痛症在内的全身性免疫反应。我们研究了硫柳汞是否会诱发在接触无机汞后在基因易感小鼠中观察到的全身性自身免疫状况。将A.SW小鼠暴露于含1.25 - 40毫克硫柳汞/升饮用水中70天。靶向34千道尔顿蛋白质纤维原蛋白的抗核仁抗体呈剂量相关模式出现，在两个最高剂量组中10天后首次出现。抗纤维原蛋白抗体的最低观察到有害作用水平（LOAEL）为2.5毫克硫柳汞/升，分别对应于147微克汞/千克体重的吸收剂量以及肾脏和淋巴结中21微克汞/克和1.9微克汞/克的浓度。组织免疫复合物沉积也发现了相同的LOAEL。硫柳汞处理的小鼠中，总血清IgE、IgG1和IgG2a浓度呈现显著的剂量相关增加，IgG1和IgE的LOAEL为5毫克硫柳汞/升，IgG2a的LOAEL为20毫克硫柳汞/升。多克隆B细胞活化呈现显著的剂量 - 反应关系，LOAEL为10毫克硫柳汞/升。因此，硫柳汞在基因易感小鼠中诱发了一种与无机汞处理后所见非常相似的全身性自身免疫综合征，尽管使用硫柳汞需要更高的汞吸收剂量。硫柳汞诱发的自身免疫综合征不同于用等效剂量甲基汞处理后观察到的较弱且更局限的自身免疫反应。
