Moldawer L L, Svaninger G, Gelin J, Lundholm K G
Department of Surgery I, Sahlgrenska Hospital, University of Gothenburg, Sweden.
Am J Physiol. 1987 Dec;253(6 Pt 1):C766-73. doi: 10.1152/ajpcell.1987.253.6.C766.
Recent studies have claimed that interleukin 1-containing preparations increase skeletal protein degradation similar to that seen during infection and inflammation. However, preparations employed have contained other products of activated macrophages, including tumor necrosis factor-alpha. In the present report, we investigated the capability of recombinant-derived murine and human interleukins 1-alpha and 1-beta and human tumor necrosis factor-alpha to affect skeletal protein synthesis and degradation both in vitro and in vivo. Partially purified products of Staphylococcus albus-stimulated human blood monocytes increased skeletal protein degradation both in vivo and in vitro. However, none of the recombinant interleukin 1 nor the human tumor necrosis factor-alpha preparations had any impact on skeletal protein balance. Both recombinant interleukin 1 and tumor necrosis factor-alpha stimulated the production of prostaglandin E2 (PGE2). Furthermore, a polyclonal antibody to human interleukin 1 eliminated the lymphoproliferative response to partially purified monocyte preparations (interleukin 1 activity), but failed to abrogate the increased skeletal protein degradation in vitro. This study demonstrates that although interleukin 1 and tumor necrosis factor-alpha induce a PGE2 response by skeletal muscle in vitro, some macrophage product distinct from either interleukin 1 or tumor necrosis factor-alpha is responsible for the accelerated skeletal protein degradation seen with partially purified human blood monocyte products. Elevated PGE2 levels do not appear to regulate skeletal protein balance in vitro.
近期研究表明，含白细胞介素1的制剂会增加骨骼蛋白降解，这与感染和炎症期间所见情况类似。然而，所使用的制剂含有活化巨噬细胞的其他产物，包括肿瘤坏死因子-α。在本报告中，我们研究了重组衍生的小鼠和人白细胞介素1-α、1-β以及人肿瘤坏死因子-α在体外和体内影响骨骼蛋白合成及降解的能力。经白色葡萄球菌刺激的人血单核细胞的部分纯化产物在体内和体外均增加了骨骼蛋白降解。然而，重组白细胞介素1制剂和人肿瘤坏死因子-α制剂均未对骨骼蛋白平衡产生任何影响。重组白细胞介素1和肿瘤坏死因子-α均刺激了前列腺素E2（PGE2）的产生。此外，抗人白细胞介素1的多克隆抗体消除了对部分纯化单核细胞制剂的淋巴细胞增殖反应（白细胞介素1活性），但未能消除体外骨骼蛋白降解的增加。本研究表明，尽管白细胞介素1和肿瘤坏死因子-α在体外可诱导骨骼肌产生PGE2反应，但部分纯化的人血单核细胞产物所致的骨骼蛋白加速降解是由不同于白细胞介素1或肿瘤坏死因子-α的某些巨噬细胞产物引起的。体外升高的PGE2水平似乎并不调节骨骼蛋白平衡。
