O. Zamir et al., REDUCED MUSCLE PROTEIN BREAKDOWN IN SEPTIC RATS FOLLOWING TREATMENT WITH INTERLEUKIN-1 RECEPTOR ANTAGONIST, International Journal of Biochemistry, 26(7), 1994, pp. 943-950
1. The role of interleukin-l (IL-I) in sepsis-induced muscle proteolys
is was assessed by treating septic rats with recombinant IL-1 receptor
antagonist (rIL-1ra). 2. In initial experiments, we tested the effect
iveness of IL-1ra in preventing muscle proteolysis induced by administ
ration of IL-1. 3. When normal rats were treated with rIL-1 alpha (thr
ee intraperitoneal doses of 100 mu g/kg body weight each over 16 hr),
total and myofibrillar muscle protein breakdown rates, measured as rel
ease of tyrosine and 3-methylhistidine, respectively, by incubated ext
ensor digitorum longus muscles, were significantly increased. 4. This
metabolic response to IL-1 alpha was completely abolished by rIL-1ra,
administered as three intraperitoneal doses of 3 mg/kg body weight eac
h over 16 hr. 5. In subsequent experiments, sepsis was induced in rats
by cecal ligation and puncture (CLP); non-septic rats were sham-opera
ted. 6. Treatment of septic rats over 16 hr with a total dose of 25 mg
/kg body weight of rIL-1ra reduced, but did not normalize, the increas
ed muscle protein breakdown rates seen during sepsis. 7. When the dose
of rIL-lra was more than doubled and given as a constant infusion at
a rate of 4.2 mg/kg body weight/hr for 16 hr, the increased rate of mu
scle proteolysis in septic rats was normalized. 8. The present study o
ffers the first direct evidence that IL-1 is involved in the regulatio
n of muscle proteolysis during sepsis.