Accelerated proteolysis of muscle is characteristic in patients with trauma or sepsis, but its cause is not well understood. Using rat muscle in vitro, we developed a bioassay to compare the proteolytic activity of plasma from 50 patients with trauma or sepsis with that of plasma from 14 normal volunteers and from 15 patients who had undergone "clean" elective surgical procedures. The mean proteolytic activity in the plasma of patients with trauma or sepsis was found to be 190 +/- 8.0 per cent of the control value (rat muscle incubated in medium alone), whereas the activity in normal plasma was 124 +/- 4.5 per cent (P less than 0.001). The activity in the plasma of patients who had undergone elective surgery was slightly elevated at 142 +/- 2.5 per cent (P less than 0.005). In 25 of the patients with trauma or sepsis the rate of amino acid release from one leg was measured by subtracting the concentration of tyrosine plus phenylalanine in the femoral artery plasma from that in the femoral vein; this rate correlated well with the bioactivity of the plasma in the bioassay system (r = 0.67, P less than 0.001). By means of ultrafiltration and chromatography, the plasma factor inducing proteolysis was isolated and found to be a peptide, probably containing sialic acid, with a chain of 33 amino acids and a molecular weight of approximately 4274 daltons.

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