Coulpier M, Andreev S, Lemercier C, Dauchel H, Lees O, Fontaine M, Ripoche J
INSERM U78, Bois-Guillaume, France.
Clin Exp Immunol. 1995 Jul;101(1):142-9. doi: 10.1111/j.1365-2249.1995.tb02290.x.
Constitutive secretion of complement C3 and factor B by the endothelial cell (EC) is lowered by therapeutic concentrations of glucocorticoids such as hydrocortisone or dexamethasone, whereas regulatory protein factor H production is increased by these hormones. In contrast, the proinflammatory cytokine IL-1 alpha has a stimulatory effect on C3 and factor B secretion by the endothelium and an inhibitory effect on factor H secretion. In this study, we examined the combined effect of IL-1 alpha and glucocorticoids on C3 and factor B expression by the endothelial cell. When dexamethasone or hydrocortisone were added to IL-1 alpha, significant potentialization of IL-1 alpha-induced stimulation of C3 and factor B production was observed, occurring at various concentrations of either stimuli. Dose-response experiments indicate that, in vitro, optimal concentrations are in the range of 10(-7) to 10(-5) M for dexamethasone and 50-200 U for IL-1 alpha. In contrast, dexamethasone counteracts, in an additive way, the inhibitory effect of IL-1 alpha on regulatory complement protein factor H production by EC. Such a potentialization between glucocorticoids and IL-1 alpha was not observed for another marker of endothelial activation, IL-1 alpha-induced stimulation of coagulation tissue factor expression. The association of glucocorticoids and IL-1 alpha therefore appears to be a specific and major stimulus for the secretion of complement C3 and factor B, two acute-phase proteins, by the endothelium. As a result of the in vitro endothelium stimulation by glucocorticoids and IL-1 alpha, C3a is generated in the vicinity of the endothelial cell. This study further suggests that complement activation, with its deleterious consequences, may result from the stimulation of endothelium in situations where high levels of IL-1 alpha and endogenous glucocorticoids coexist, such as in septic shock.
内皮细胞（EC）对补体C3和B因子的组成性分泌会被治疗浓度的糖皮质激素（如氢化可的松或地塞米松）降低，而这些激素会增加调节蛋白H因子的产生。相反，促炎细胞因子IL-1α对内皮细胞分泌C3和B因子有刺激作用，而对H因子分泌有抑制作用。在本研究中，我们检测了IL-1α和糖皮质激素对内皮细胞C3和B因子表达的联合作用。当将地塞米松或氢化可的松添加到IL-1α中时，观察到IL-1α诱导的C3和B因子产生刺激有显著的增强，在两种刺激物的不同浓度下均会出现。剂量反应实验表明，在体外，地塞米松的最佳浓度范围为10^(-7)至10^(-5) M，IL-1α为50 - 200 U。相反，地塞米松以相加的方式抵消了IL-1α对内皮细胞调节性补体蛋白H因子产生的抑制作用。对于内皮细胞活化的另一个标志物，即IL-1α诱导的凝血组织因子表达的刺激，未观察到糖皮质激素和IL-1α之间的这种增强作用。因此，糖皮质激素和IL-1α的联合似乎是内皮细胞分泌补体C3和B因子这两种急性期蛋白的一种特异性且主要的刺激因素。由于糖皮质激素和IL-1α对体外内皮细胞的刺激，在内皮细胞附近会产生C3a。本研究进一步表明，补体激活及其有害后果可能源于在IL-1α和内源性糖皮质激素高水平共存的情况下（如在脓毒症休克中）对内皮细胞的刺激。
