Zeidel M L, Brady H R, Kohan D E
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Am J Physiol. 1991 Dec;261(6 Pt 2):F1013-6. doi: 10.1152/ajprenal.1991.261.6.F1013.
Interleukin-1 (IL-1), a cytokine produced by macrophages, causes an increase in Na+ excretion in experimental animals. Micropuncture studies have determined that the natriuretic effect of IL-1 is largely due to inhibition of Na+ reabsorption in the collecting duct. The current studies made use of suspensions of rabbit inner medullary collecting duct (IMCD) cells to examine the mechanism by which IL-1 regulates Na+ transport. IL-1 reduced ouabain-sensitive 86Rb+ uptake by 48% at 10 s, 36% at 30 s, and 29% at 60 s, suggesting an inhibitory effect on Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity. IL-1 inhibition of 86Rb+ uptake occurred in a dose-dependent manner. This effect appears to be mediated by prostaglandin E2 (PGE2) because 1) ibuprofen blocks the inhibitory effect of IL-1 on IMCD Na(+)-K(+)-ATPase activity, 2) IL-1 and PGE2 cause equivalent and nonadditive inhibition of 86Rb+ uptake, 3) IL-1 causes a two- to threefold increase in PGE2 content in IMCD cells, and 4) dose-response curves were similar for IL-1 stimulation of PGE2 content and inhibition of 86Rb+ uptake in IMCD cells. Thus the natriuretic effect of IL-1 is due, at least in part, to stimulation of PGE2 production by collecting duct cells with resultant inhibition of Na(+)-K(+)-ATPase activity.
白细胞介素-1（IL-1）是一种由巨噬细胞产生的细胞因子，可使实验动物的钠排泄增加。微穿刺研究已确定，IL-1的利钠作用主要是由于抑制了集合管对钠的重吸收。目前的研究利用兔髓质内层集合管（IMCD）细胞悬液来研究IL-1调节钠转运的机制。IL-1使哇巴因敏感的86Rb+摄取在10秒时降低48%，30秒时降低36%，60秒时降低29%，提示对钠钾-腺苷三磷酸酶（ATP酶）活性有抑制作用。IL-1对86Rb+摄取的抑制呈剂量依赖性。这种作用似乎是由前列腺素E2（PGE2）介导的，因为：1）布洛芬可阻断IL-1对IMCD钠钾-ATP酶活性的抑制作用；2）IL-1和PGE2对86Rb+摄取产生同等且无相加性的抑制作用；3）IL-1使IMCD细胞中PGE2含量增加两到三倍；4）IL-1刺激PGE2含量和抑制IMCD细胞中86Rb+摄取的剂量反应曲线相似。因此，IL-1的利钠作用至少部分是由于集合管细胞产生PGE2增加，从而抑制了钠钾-ATP酶活性。
