糖皮质激素治疗SLE不反应的分子机制

Molecular mechanisms underlying corticosteroid unresponsiveness in the treatment of systemic lupus erythematosus

SLE治疗过程中，糖皮质激素的治疗不反应是目前临床遇到的棘手问题。近年来的研究发现，SLE外周血活化淋巴细胞膜表面P-糖蛋白的高表达，促使进入淋巴细胞内的糖皮质激素被泵出或巨噬细胞移动抑制因子自分泌增加，拮抗激素的抗炎活性，共同参与诱导SLE患者对激素治疗的不反应。抑制或下调淋巴细胞P-糖蛋白活性和巨噬细胞移动抑制因子的表达，有可能促使临床逆转对激素治疗的抵抗。

It is an awkward issue to treat systemic lupus erythematosus （SLE） in patients with corticosteroid unresponsiveness. Recently, P-glycoprotein （P-gp） and macrophage migration inhibition factor （MIF） have been clearly linked to the modulation of corticosteroid sensitivity. The following two mechanisms seem to be involved in corticosteroid unresponsiveness. First, over-expression of P-gp on activated peripheral lymphocytes can cause the exclusion of intercellular cortieosteroid from lymphocytes. Second, the expression of MIF, which exerts a potent antagonistic effect on corticosteroid suppression of immune-mediated inflammation, is increased in patients with SLE. It may restore the sensitivity to corticosteroid to down-regulate or suppress the expression of P-gp and MIF in patients with SLE.