Bourrié B, Benoît J M, Derocq J M, Esclangon M, Thomas C, Le Fur G, Casellas P
Sanofi Recherche, Department of Immunopharmacology, Montpellier, France.
Immunology. 1996 Jul;88(3):389-93. doi: 10.1046/j.1365-2567.1996.d01-657.x.
Sigma receptors originally described in distinct regions of the central nervous system are expressed on cells of the immune system. A sigma ligand, SR 31747A, was observed here to inhibit in vitro the Staphylococcal enterotoxin B (SEB)-driven lymphocyte proliferation. In mice, the drug confers a potent protection against the lethality induced by SEB, stimulates the SEB-induced serum release of interleukin (IL)-10 and inhibits at the same time the systemic release of IL-2, IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6 and tumour necrosis factor-alpha (TNF-alpha). The enhancement of IL-10 production by this compound is also effective in nude mice treated with SEB, indicating that IL-10 of T-cell origin is not involved in this process. The finding that a sigma ligand protects against the SEB-induced toxicity provides insights into the clinical use of this family of compounds, particularly in food poisoning and septic shock where Staphylococcal enterotoxins are involved. The observation that this compound stimulates IL-10 synthesis indicates that it could be a potent regulatory agent of chronic inflammatory diseases.
最初在中枢神经系统不同区域被描述的西格玛受体在免疫系统细胞上表达。在此观察到一种西格玛配体SR 31747A在体外可抑制葡萄球菌肠毒素B（SEB）驱动的淋巴细胞增殖。在小鼠中，该药物对SEB诱导的致死性具有强大的保护作用，刺激SEB诱导的白细胞介素（IL）-10血清释放，同时抑制IL-2、IL-4、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、IL-6和肿瘤坏死因子-α（TNF-α）的全身释放。该化合物对IL-10产生的增强作用在用SEB处理的裸鼠中也有效，表明T细胞来源的IL-10不参与此过程。西格玛配体可预防SEB诱导的毒性这一发现为该类化合物的临床应用提供了见解，尤其是在涉及葡萄球菌肠毒素的食物中毒和败血症休克中。该化合物刺激IL-10合成的观察结果表明它可能是慢性炎症性疾病的有效调节剂。
