Muscle Wasting and IL - 6

Muscle wasting is a common feature of systemic inflammation and malignant diseases. The primary cause is accelerated proteolysis. Protein degradation was found to be accelerated by IL-6 with activation of intracellular proteases in C2C12 myotubes. IL-6 transgenic mice displayed extensive muscle wasting together with an increase of proteolytic pathways. The increase in activities and mRNA levels of cathepsins (B and L) and the poly-ubiquitin (Ub) mRNA level could be inhibited by treatment with IL-6 receptor antibody (MR16-1), which inhibits the binding of IL-6 to the receptor. Muscle wasting and an increase in the serum IL6 level were observed with Colon-26 adenocarcinoma. This muscle wasting and increases in the activity and mRNA level of cathepsin L and the poly-Ub mRNA level could be inhibited by MR16-1 treatment via inhibiting the action of IL-6. IL-6 production and atrophy of muscle fibers were induced by intramuscular injection of turpentine oil. The injected muscle displayed increased activities and mRNA levels of cathepsins (B,L). The treatment with MR16-1 suppressed the increase of cathepsin activities. IL-6 is considered to be a proteolysis-inducing factor due to its modulation of muscle proteolytic systems. IL-6 plays a pivotal role in the muscle wasting observed in systemic inflammation, cancer cachexia and inflammed muscle.