Diez R A, Mistchenko A S, Falcoff E T
Unité 196 INSERM, Institut Curie, Section de Biologie, Paris, France.
Immunopharmacol Immunotoxicol. 1987;9(1):115-28. doi: 10.3109/08923978709035205.
To investigate possible mechanisms of interaction between corticosteroids and interferons (IFNs), the specific binding of recombinant human IFNs alpha 2 and alpha in Namalva cells after 72 h culture with dexamethasone (10(-8) M to 10(-6) M) was evaluated. Exponentially growing cells were incubated with different concentrations of the radiolabelled IFNs, with or without an excess of unlabelled IFN. The parameters of the interaction between each IFN and its specific receptor were analyzed by the Scatchard method. In the dose range tested, dexamethasone induced a dose-dependent inhibition of Namalva cells growth, which reached about 35% at 10(-6) M. The specific binding of IFN-alpha 2 was decreased to a maximum of 40%, for dexamethasone concentrations greater than or equal to 10(-7) M. The decrease in binding induced by the corticoid was additive with the down-regulation induced by IFN-alpha 2 itself. On the contrary, the specific binding of IFN-alpha was increased by dexamethasone in a dose-dependent fashion within the tested range. The maximal increase in the number of sites per cell was about 60%, with a slight decrease in affinity. These results suggest that complex interactions might arise between corticosteroids and IFNs in the course of their clinical use.
为了研究皮质类固醇与干扰素（IFN）之间可能的相互作用机制，评估了地塞米松（10⁻⁸M至10⁻⁶M）培养72小时后Namalva细胞中重组人IFNα2和α的特异性结合。将指数生长的细胞与不同浓度的放射性标记IFN孵育，有或没有过量的未标记IFN。通过Scatchard方法分析每种IFN与其特异性受体之间相互作用的参数。在所测试的剂量范围内，地塞米松诱导Namalva细胞生长呈剂量依赖性抑制，在10⁻⁶M时达到约35%。对于地塞米松浓度大于或等于10⁻⁷M，IFN-α2的特异性结合最多降低至40%。皮质类固醇诱导的结合减少与IFN-α2自身诱导的下调相加。相反，在测试范围内，地塞米松以剂量依赖性方式增加IFN-α的特异性结合。每个细胞位点数量的最大增加约为60%，亲和力略有下降。这些结果表明，皮质类固醇和IFN在临床使用过程中可能会出现复杂的相互作用。
