Third Department of Internal Medicine Gunma University School of Medicine Japan.
Mediators Inflamm. 1994;3(5):375-80. doi: 10.1155/S0962935194000529.
The effect of FK506 and cyclosporin A (CsA) on the production of interleukin 6 (IL-6) in adherent monocytes was studied at a single-cell level by the avidinbiotin- peroxidase complex methods. The percentage of IL-6-producing monocytes increased when stimulated with lipopolysaccharide (LPS) at concentrations between 10 ng/ml and 10 mug/ml, in a dose dependent manner. Both FK506 and CsA enhanced the percentage of IL-6- producing monocytes stimulated with 100 pg/ml-1 mug/ml of LPS up to values near those obtained with 10 mug/ml of LPS. The enhancement by FK506 and CsA was not seen when monocytes were stimulated with a high concentration of LPS (10 mug/ml). When monocytes were stimulated with a low concentration of LPS (10 ng/ml), FK506 and CsA enhanced IL-6 production in a dose dependent manner, at a drug concentration of 0.12 nM-1.2 muM (0.1-1 000 ng/ml) for FK506 and 0.83 nM-8.3 muM (1-10 000 ng/ml) for CsA. The optimal effect of FK506 was achieved at a concentration 7-fold lower than that of CsA. In contrast, production of turnout necrosis factor-alpha (TNFalpha and interleukin 1beta (IL-1beta) was slightly suppressed by FK506 and CsA at the concentrations tested. Moreover, pretreatment of monocytes with FK506 and CsA had a significant enhancing effect on LPS-induced IL-6 production, while treatment with FK506 or CsA after LPS stimulation had no effects on IL-6 production, suggesting that the enhancing effect of each drug is exerted before LPS stimulation or at an early stage of the post-receptor pathway after LPS stimulation. These experiments demonstrate that FK506 and CsA can selectively enhance IL-6 production in monocytes under certain conditions in vitro and, possibly, also in vivo.
采用亲和素-生物素-过氧化物酶复合物法，在单细胞水平上研究了 FK506 和环孢素 A（CsA）对贴壁单核细胞白细胞介素 6（IL-6）产生的影响。当用浓度在 10ng/ml 到 10ug/ml 之间的脂多糖（LPS）刺激时，IL-6 产生单核细胞的比例以剂量依赖的方式增加。FK506 和 CsA 均增强了 100pg/ml-1ug/ml LPS 刺激的 IL-6 产生单核细胞的比例，接近 10ug/ml LPS 获得的值。当用高浓度 LPS（10ug/ml）刺激单核细胞时，FK506 和 CsA 没有增强作用。当用低浓度 LPS（10ng/ml）刺激单核细胞时，FK506 和 CsA 以剂量依赖的方式增强 IL-6 的产生，FK506 的药物浓度为 0.12nM-1.2uM（0.1-1000ng/ml），CsA 的药物浓度为 0.83nM-8.3uM（1-10000ng/ml）。FK506 的最佳效果是在浓度比 CsA 低 7 倍的情况下实现的。相比之下，FK506 和 CsA 在测试浓度下略微抑制肿瘤坏死因子-α（TNFalpha）和白细胞介素 1beta（IL-1beta）的产生。此外，FK506 和 CsA 预处理单核细胞对 LPS 诱导的 IL-6 产生有显著增强作用，而 LPS 刺激后用 FK506 或 CsA 处理对 IL-6 产生没有影响，表明每种药物的增强作用是在 LPS 刺激之前或在 LPS 刺激后的受体后途径的早期发挥的。这些实验表明，FK506 和 CsA 可以在某些条件下选择性地增强单核细胞中 IL-6 的产生，并且可能在体内也是如此。
