Kita H, Mayeno A N, Weyand C M, Goronzy J J, Weiler D A, Lundy S K, Abrams J S, Gleich G J
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
J Allergy Clin Immunol. 1995 Jun;95(6):1261-7. doi: 10.1016/s0091-6749(95)70084-6.
The eosinophilia-myalgia syndrome, caused by a contaminant or contaminants in epidemiologically implicated L-tryptophan products, is characterized by eosinophilia and eosinophil degranulation. We hypothesized that immune cells are stimulated by implicated L-tryptophan and produce eosinophil-active cytokines.
This study was designed to identify substances in L-tryptophan causing the eosinophilia-myalgia syndrome.
Peripheral blood mononuclear cells were cultured with L-tryptophan products, and supernatants were tested for their ability to enhance eosinophil degranulation and survival in vitro and for their cytokine content. Subsequently, 46 different L-tryptophan lots were analyzed for their in vitro biologic activities.
After peripheral blood mononuclear cells were cultured with implicated L-tryptophan, their supernatants enhanced eosinophil degranulation and survival. These activities were blocked by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody; immunoreactive GM-CSF was measurable in the supernatants. Monocytes, but not T lymphocytes, were the responding cells. However, no correlation was observed between the in vitro biologic activity and lots of epidemiologically implicated L-tryptophan products. This biologic activity in the L-tryptophan products was characterized as endotoxin.
Although L-tryptophan products stimulate peripheral blood mononuclear cells to produce GM-CSF, this response is caused by endotoxin contamination of the L-tryptophan products and not by a specific L-tryptophan contaminant. Endotoxin contamination must be considered as a possible cause of eosinophil-active cytokine production by peripheral blood mononuclear cells.
嗜酸性粒细胞增多性肌痛综合征由流行病学上涉及的L-色氨酸产品中的一种或多种污染物引起，其特征为嗜酸性粒细胞增多和嗜酸性粒细胞脱颗粒。我们推测免疫细胞受到相关L-色氨酸的刺激并产生嗜酸性粒细胞活性细胞因子。
本研究旨在鉴定L-色氨酸中导致嗜酸性粒细胞增多性肌痛综合征的物质。
将外周血单个核细胞与L-色氨酸产品一起培养，检测上清液在体外增强嗜酸性粒细胞脱颗粒和存活的能力及其细胞因子含量。随后，分析了46个不同批次的L-色氨酸的体外生物学活性。
外周血单个核细胞与相关L-色氨酸一起培养后，其上清液增强了嗜酸性粒细胞脱颗粒和存活能力。这些活性被抗粒细胞-巨噬细胞集落刺激因子（GM-CSF）抗体阻断；上清液中可检测到免疫反应性GM-CSF。起反应的细胞是单核细胞，而非T淋巴细胞。然而，在体外生物学活性与流行病学上涉及的L-色氨酸产品批次之间未观察到相关性。L-色氨酸产品中的这种生物学活性被鉴定为内毒素。
尽管L-色氨酸产品刺激外周血单个核细胞产生GM-CSF，但这种反应是由L-色氨酸产品的内毒素污染引起的，而非特定的L-色氨酸污染物。内毒素污染必须被视为外周血单个核细胞产生嗜酸性粒细胞活性细胞因子的一个可能原因。
