Frondoza C, Jones L, Rose N R, Hatakeyama A, Phelps R, Bona C
Johns Hopkins Dept. of Molecular Microbiology and Immunology, Baltimore, Maryland 21239, USA.
J Autoimmun. 1996 Aug;9(4):473-83. doi: 10.1006/jaut.1996.0064.
Several reports have implicated an association between the development of connective tissue disorders and exposure to silicone in breast implant patients. These connective tissue disorders include local or systemic scleroderma-like syndrome and have been characterized by fibrosis as well as the presence of circulating autoantibodies. Whether silicone does potentiate the development of a scleroderma-like syndrome is still to be defined. The purpose of the present study was to determine the effect of silicone on the tight skin (TSK/+) mouse which develops a scleroderma-like syndrome and on its normal pa/pa TSK/- littermate. Groups of six TSK and five of their normal pa/pa littermates were injected subcutaneously with low molecular weight silicone (LMW-PDMS), high molecular weight silicone gel (HMW-PDMS), incomplete Freunds' adjuvant (IFA) or Hank's balanced salt solution (HBSS) in the dorsal neck area and ventrally in the upper chest region. Serum was obtained prior to and 1 month after injection of silicone, IFA, or control HBSS. Antibody levels to bovine serum albumin (BSA), RNA polymerase (RNAP) and topoisomerase I were determined. Mice were then euthanized and strips of skin from the injection sites as well as samples of kidney and liver were studied histologically. No significant pathological changes were observed in TSK/- mice 1 month following injection with HBSS, LMW-PDMS or HMW-PDMS. Skin samples from TSK/+ mice which received LMW-PDMS showed hyperplasia of the dermis and peri-panniculus carnosus tissue and infiltrates of macrophages containing lipid-like vacuolated materials. Lipid vacuoles were observed throughout the deeper dermis as multiple loculated vacuoles. TSK mice which received HMW-PDMS showed similar thickening of the dermis and the peri-panniculus carnosus connective tissue. There were no significant differences in the histologic characteristics of the silicone-injected TSK/+ mice compared to those that received HBSS or IFA. No detectable changes in the kidney, spleen, or liver samples taken from TSK/+ or TSK/- mice injected with HBSS, IFA or silicone (LMW-PDMS, HMW-PDMS) preparations were noted. Baseline circulating antibody levels to BSA, RNAP and topoisomerase were significantly higher in TSK/+ mice compared to the control TSK/- littermates. Administration of silicone (LMW-PDMS or HMW-PDMS) did not significantly alter circulating antibody levels to BSA, RNAP and topoisomerase in either the TSK/+ or the TSK/- mice. The results of this study indicate that silicone administration does not potentiate the development of the scleroderma-syndrome characterized by skin lesions and presence of circulating antibodies in the TSK/+ model.
几份报告表明，在接受乳房植入物的患者中，结缔组织疾病的发生与接触硅酮之间存在关联。这些结缔组织疾病包括局部或全身性硬皮病样综合征，其特征为纤维化以及循环自身抗体的存在。硅酮是否确实会促进硬皮病样综合征的发展仍有待确定。本研究的目的是确定硅酮对发生硬皮病样综合征的紧皮（TSK/+）小鼠及其正常的pa/pa TSK/-同窝小鼠的影响。将六只TSK小鼠及其五只正常的pa/pa同窝小鼠分为几组，在其颈部背侧区域和上胸部腹侧皮下注射低分子量硅酮（LMW-PDMS）、高分子量硅胶（HMW-PDMS）、不完全弗氏佐剂（IFA）或汉克平衡盐溶液（HBSS）。在注射硅酮、IFA或对照HBSS之前以及注射后1个月采集血清。测定针对牛血清白蛋白（BSA）、RNA聚合酶（RNAP）和拓扑异构酶I的抗体水平。然后对小鼠实施安乐死，并对注射部位的皮肤条以及肾脏和肝脏样本进行组织学研究。在注射HBSS、LMW-PDMS或HMW-PDMS后1个月，TSK/-小鼠未观察到明显的病理变化。接受LMW-PDMS的TSK/+小鼠的皮肤样本显示真皮和肉膜周组织增生，以及含有脂质样空泡物质的巨噬细胞浸润。在整个深层真皮中观察到脂质空泡为多个分隔的空泡。接受HMW-PDMS的TSK小鼠显示真皮和肉膜周结缔组织有类似的增厚。与接受HBSS或IFA的小鼠相比，注射硅酮的TSK/+小鼠的组织学特征没有显著差异。在注射HBSS、IFA或硅酮（LMW-PDMS、HMW-PDMS）制剂的TSK/+或TSK/-小鼠采集的肾脏、脾脏或肝脏样本中未发现可检测到的变化。与对照TSK/-同窝小鼠相比，TSK/+小鼠中针对BSA、RNAP和拓扑异构酶的基线循环抗体水平显著更高。给予硅酮（LMW-PDMS或HMW-PDMS）并未显著改变TSK/+或TSK/-小鼠中针对BSA、RNAP和拓扑异构酶的循环抗体水平。本研究结果表明，在TSK/+模型中，给予硅酮不会促进以皮肤病变和循环抗体存在为特征的硬皮病综合征的发展。
