Moog C, Luu B, Beck J P, Italiano L, Bischoff P
Laboratoire de Chimie Organique des Substances Naturelles, UA 31, CNRS, Strasbourg, France.
Int J Immunopharmacol. 1988;10(5):511-8. doi: 10.1016/0192-0561(88)90067-7.
Several oxysterols are powerful immunosuppressors. Among them 7,25-dihydroxycholesterol (7,25-OHC) seems to be particularly interesting. The effect of this synthetic sterol on murine lymphocytes, stimulated by Con A, or by allogeneic or TNP-modified syngeneic lymphocytes, was investigated. The results showed that the induction of cytotoxic T-lymphocytes (CTL) was strongly inhibited by a treatment with non-toxic concentrations of this sterol. A marked reduction of interleukin 2 (IL-2) production by alloantigen stimulated lymphocytes occurred at the same concentrations. We also showed that receptors to IL-2 did not appear on lymphocytes stimulated by Con A, when 7,25-OHC was added at the beginning of the culture. The addition of exogenous IL-2 to the culture was found to only slightly reverse the inhibition caused by 7,25-OHC. Taken together, these results indicate that an impairment at the early steps of lymphocyte activation, involving IL-2 secretion, could be responsible, at least in part for the various immunosuppressive effects of 7,25-OHC.
几种氧化甾醇是强效免疫抑制剂。其中，7,25-二羟基胆固醇（7,25-OHC）似乎特别引人关注。研究了这种合成甾醇对由刀豆蛋白A（Con A）、同种异体淋巴细胞或经三硝基苯（TNP）修饰的同基因淋巴细胞刺激的小鼠淋巴细胞的作用。结果表明，用无毒浓度的这种甾醇处理可强烈抑制细胞毒性T淋巴细胞（CTL）的诱导。在相同浓度下，同种抗原刺激的淋巴细胞产生的白细胞介素2（IL-2）明显减少。我们还表明，当在培养开始时添加7,25-OHC时，由Con A刺激的淋巴细胞上未出现IL-2受体。向培养物中添加外源性IL-2仅略微逆转了7,25-OHC引起的抑制作用。综上所述，这些结果表明，淋巴细胞激活早期步骤的损伤，涉及IL-2分泌，可能至少部分地导致了7,25-OHC的各种免疫抑制作用。
