Porat R, Poutsiaka D D, Miller L C, Granowitz E V, Dinarello C A
Department of Medicine, New England Medical Center, Boston, Massachusetts 02111.
FASEB J. 1992 Apr;6(7):2482-6. doi: 10.1096/fasebj.6.7.1532945.
Interleukin-1 (IL-1) is a potent stimulator of IL-8 production by fibroblasts and monocytes. In the present study, we asked how much of endotoxin (LPS)-induced IL-8 production by human peripheral blood mononuclear cells was due to IL-1 induced by LPS. Cells were stimulated with either IL-1 beta, LPS, or Borrelia burgdorferi, and total IL-8 was determined by a specific radioimmunoassay. The addition of saturating concentrations of IL-1 receptor antagonist protein (IRAP) reduced the IL-1 beta-, LPS-, and B. burgdorferi-induced IL-8 synthesis by 85, 50, and 40%, respectively. Increasing the concentration of LPS did not affect the reduction in IL-8 synthesis observed in the presence of IRAP. Significant inhibition of the IL-1 beta-induced IL-8 synthesis was observed when IRAP was added 60 or 90 min after IL-1 beta; similarly, IL-8 synthesis after LPS was also reduced by delayed addition of IRAP. These data suggest that the ameliorative effects of IL-1 receptor blockade in models of inflammation and infection may be due, in part, to suppression of IL-1-induced IL-8.
白细胞介素-1（IL-1）是成纤维细胞和单核细胞产生IL-8的有效刺激物。在本研究中，我们探究了人类外周血单个核细胞中内毒素（LPS）诱导产生的IL-8有多少是由LPS诱导的IL-1所致。用IL-1β、LPS或伯氏疏螺旋体刺激细胞，通过特异性放射免疫测定法测定总的IL-8。添加饱和浓度的IL-1受体拮抗剂蛋白（IRAP）可分别使IL-1β、LPS和伯氏疏螺旋体诱导的IL-8合成减少85%、50%和40%。增加LPS的浓度并不影响在IRAP存在时观察到的IL-8合成减少。在IL-1β加入60或90分钟后添加IRAP，可观察到对IL-1β诱导的IL-8合成有显著抑制作用；同样，延迟添加IRAP也可降低LPS刺激后的IL-8合成。这些数据表明，IL-1受体阻断在炎症和感染模型中的改善作用可能部分归因于对IL-1诱导的IL-8的抑制。
