Love L A, Rader J I, Crofford L J, Raybourne R B, Principato M A, Page S W, Trucksess M W, Smith M J, Dugan E M, Turner M L
Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, District of Columbia 20204.
J Clin Invest. 1993 Mar;91(3):804-11. doi: 10.1172/JCI116300.
The eosinophilia-myalgia syndrome (EMS) has been associated with ingestion of L-tryptophan (L-TRP) produced by a single manufacturer. Epidemiological data implicated 1,1'-ethylidenebis (L-tryptophan) (EBT) (peak 97 or peak E) as a possible etiologic agent. We showed previously that Lewis rats treated with the L-TRP implicated in EMS develop fasciitis and perimyositis similar to those seen in human EMS. We now report the pathology associated with the treatment of Lewis rats with synthetic EBT and/or L-TRP. All animals treated for 6 wk with case-associated L-TRP or EBT developed significant myofascial thickening, compared with animals in the vehicle control and control L-TRP groups. However, even those animals receiving the control L-TRP showed a mild but significant increase in the thickness of the myofascia, compared with vehicle-treated control animals. All animals except vehicle controls also exhibited significant pancreatic pathology, including fibrosis and acinar changes. Only animals treated with case-associated L-TRP for 6 wk showed evidence of immune activation with increased frequency of CD8, Ia, and IL-2 receptor-positive cells in the peripheral blood. Animals receiving L-TRP or EBT for < 6 wk did not show significant differences in myofascial thickness, although these animals did show pancreatic acinar changes. Although these results demonstrate for the first time the pathological effects of EBT, they do not rule out the possibility that other impurities in the EMS-case-associated L-TRP may also contribute to some of the features of EMS.
嗜酸性粒细胞增多性肌痛综合征（EMS）与食用由单一制造商生产的L-色氨酸（L-TRP）有关。流行病学数据表明1,1'-亚乙基双（L-色氨酸）（EBT）（峰值97或峰值E）可能是病因。我们之前表明，用与EMS相关的L-TRP处理的Lewis大鼠会出现与人类EMS中所见相似的筋膜炎和肌炎。我们现在报告用合成EBT和/或L-TRP处理Lewis大鼠的相关病理学。与赋形剂对照组和对照L-TRP组的动物相比，所有用与病例相关的L-TRP或EBT处理6周的动物均出现明显的肌筋膜增厚。然而，与赋形剂处理的对照动物相比，即使是那些接受对照L-TRP的动物，其肌筋膜厚度也有轻微但显著的增加。除赋形剂对照组外，所有动物还表现出明显的胰腺病理学变化，包括纤维化和腺泡改变。只有用与病例相关的L-TRP处理6周的动物显示出免疫激活的证据，外周血中CD8、Ia和IL-2受体阳性细胞的频率增加。接受L-TRP或EBT处理时间小于6周的动物，其肌筋膜厚度没有显著差异，尽管这些动物确实出现了胰腺腺泡变化。尽管这些结果首次证明了EBT的病理作用，但它们并不排除与EMS病例相关的L-TRP中的其他杂质也可能导致EMS某些特征的可能性。
