Sepsis in mice stimulates muscle proteolysis in the absence of IL-6

We tested the role of interleukin-6 (IL-6) in sepsis-induced muscle proteol ysis by determining ubiquitin mRNA levels and protein breakdown rates in in cubated extensor digitorum longus muscles from septic and sham-operated IL- 6 knockout and wild-type mice. In addition, the effect of treatment of mice with human recombinant IL-6 on muscle protein breakdown rates was determin ed. Finally, protein breakdown rates were measured in myotubes treated for up to 48 h with different concentrations of IL-6. Sepsis in wild-type mice resulted in an approximately ninefold increase in plasma IL-6 levels, where as IL-6 was not detectable in plasma of sham-operated or septic IL-6 knocko ut mice. Total and myofibrillar muscle protein breakdown rates were increas ed by similar to 30% and threefold, respectively, in septic IL-6 wild-type mice with an almost identical response noted in septic IL-6 knockout mice. Ubiquitin mRNA levels determined by dot blot analysis were increased during sepsis in muscles from both IL-6 knockout and wild-type mice, although the increase was less pronounced in IL-6 knockout than in wild-type mice. Trea tment of normal mice or of cultured L6 myotubes with IL-6 did not influence protein breakdown rates. The present results suggest that IL-6 does not re gulate muscle proteolysis during sepsis.