Tsujinaka T, Fujita J, Ebisui C, Yano M, Kominami E, Suzuki K, Tanaka K, Katsume A, Ohsugi Y, Shiozaki H, Monden M
Department of Surgery II, Osaka University Medical School, Suita, Japan.
J Clin Invest. 1996 Jan 1;97(1):244-9. doi: 10.1172/JCI118398.
The muscles of IL-6 transgenic mice suffer from atrophy. Experiments were carried out on these transgenic mice to elucidate activation of proteolytic systems in the gastrocnemius muscles and blockage of this activation by treatment with the anti-mouse IL-6 receptor (mIL-6R) antibody. Muscle atrophy observed in 16-wk-old transgenic mice was completely blocked by treatment with the mIL-6R antibody. In association with muscle atrophy, enzymatic activities and mRNA levels of cathepsins (B and L) and mRNA levels of ubiquitins (poly- and mono-ubiquitins) increased, whereas the mRNA level of muscle-specific calpain (calpain 3) decreased. All these changes were completely eliminated by treatment with the mIL-6R antibody. This IL-6 receptor antibody could, therefore, be effective against muscle wasting in sepsis and cancer cachexia, where IL-6 plays an important role.
白细胞介素-6转基因小鼠的肌肉会出现萎缩。对这些转基因小鼠进行了实验，以阐明腓肠肌中蛋白水解系统的激活情况，以及用抗小鼠白细胞介素-6受体（mIL-6R）抗体处理对这种激活的阻断作用。用mIL-6R抗体处理可完全阻断16周龄转基因小鼠中观察到的肌肉萎缩。与肌肉萎缩相关的是，组织蛋白酶（B和L）的酶活性和mRNA水平以及泛素（多聚泛素和单泛素）的mRNA水平升高，而肌肉特异性钙蛋白酶（钙蛋白酶3）的mRNA水平降低。用mIL-6R抗体处理可完全消除所有这些变化。因此，这种白细胞介素-6受体抗体可能对脓毒症和癌症恶病质中的肌肉消耗有效，在这些病症中白细胞介素-6起着重要作用。
