Pratta M A, Di Meo T M, Ruhl D M, Arner E C
E. I. Du Pont de Nemours & Co., Medical Products Department, Wilmington, DE 19880-0440.
Agents Actions. 1989 Jun;27(3-4):250-3. doi: 10.1007/BF01972788.
The activities of recombinant interleukin-1-beta (IL-1) and recombinant tumor necrosis factor-alpha (TNF) on cartilage proteoglycan metabolism were compared in an organ culture system. IL-1, 1 to 100 ng/ml, and TNF, 10 to 1,000 ng/ml, increased proteoglycan degradation. The concentration-response curves were parallel. The timecourse for degradation was similar for the two cytokines during a 6 day incubation. Both cytokines inhibited the synthesis of new proteoglycan as measured by 35S incorporation. The inhibition curves were parallel and concentration-related between 1 and 10 ng/ml for IL-1 and between 10 and 100 ng/ml for TNF. Maximal inhibition was 60% in the presence of IL-1 (10 ng/ml) or TNF (100 ng/ml), and plateaued at higher concentrations. IL-1 was ten fold more potent than TNF in stimulating proteoglycan breakdown and inhibiting proteoglycan synthesis. Degradation in response to TNF, but not to IL-1, could be blocked by a polyclonal antibody to TNF. A polyclonal antibody to IL-1 could block proteoglycan breakdown in response to both cytokines suggesting that TNF may be mediating proteoglycan degradation by inducing the production of interleukin-1.
在器官培养系统中比较了重组白细胞介素-1β（IL-1）和重组肿瘤坏死因子-α（TNF）对软骨蛋白聚糖代谢的作用。1至100 ng/ml的IL-1和10至1000 ng/ml的TNF均可增加蛋白聚糖降解。浓度-反应曲线呈平行关系。在6天的孵育过程中，两种细胞因子的降解时间进程相似。两种细胞因子均抑制通过35S掺入法测定的新蛋白聚糖的合成。抑制曲线呈平行关系，且与浓度相关，IL-1在1至10 ng/ml之间，TNF在10至100 ng/ml之间。在存在IL-1（10 ng/ml）或TNF（100 ng/ml）的情况下，最大抑制率为60%，且在更高浓度时达到平台期。在刺激蛋白聚糖分解和抑制蛋白聚糖合成方面，IL-1的效力比TNF高10倍。针对TNF的多克隆抗体可阻断对TNF而非IL-1的反应所导致的降解。针对IL-1的多克隆抗体可阻断对两种细胞因子的反应所导致的蛋白聚糖分解，这表明TNF可能通过诱导白细胞介素-1的产生来介导蛋白聚糖降解。
