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 proteolysis by determining ubiquitin mRNA levels and protein breakdown rates in incubated 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 determined. 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, whereas IL-6 was not detectable in plasma of sham-operated or septic IL-6 knockout mice. Total and myofibrillar muscle protein breakdown rates were increased by approximately 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. Treatment 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 regulate muscle proteolysis during sepsis.
Williams
A
A
Department of Surgery, University of Cincinnati, and Shriners Hospital for Children, Cincinnati, Ohio 45267, USA.
Wang
J J
JJ
Wang
L
L
Sun
X
X
Fischer
J E
JE
Hasselgren
P O
PO
D000818:Animals; D006801:Humans; D007239:Infections / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout / Q000235:genetics; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D012016:Reference Values; D014452:Ubiquitins / Q000235:genetics
D015850:Interleukin-6; D009124:Muscle Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014452:Ubiquitins; D010447:Peptide Hydrolases