Effect of plasma from cancer patients on rat skeletal muscle protein degradation and PGE2 release in vitro.
Cachexia in tumour-bearing patients involves loss of skeletal muscle proteins. In order to elucidate the mechanisms underlying this phenomenon, we tested the hypothesis of the presence of a circulating proteolytic factor (possibly interleukin-1, acting through an increased PGE2 release) in the plasma of cancer patients, because such a mechanism has been demonstrated in patients with sepsis or trauma and in animals with bacteraemia or viraemia. The effect of plasma from 13 malnourished cancer patients and 14 controls on PGE2 release and protein degradation (assessed as Tyr release) in rat diaphragm in vitro was evaluated; human recombinant interleukin-1 alpha (IL-1) was used for comparison. IL-1 increased PGE2 release (+44% at 5 U/ml), but did not greatly affect proteolysis. On the contrary, human plasma (125 microliters/ml) from both control and tumour-bearing individuals did not affect PGE2 release significantly, but greatly reduced Tyr release. The decrease in Tyr release by plasma was dose-dependent. In conclusion, our data indicate that, at variance with what was demonstrated in patients with trauma or sepsis, loss of skeletal muscle proteins in cancer patients is not mediated by a circulating factor. In addition, evidence is provided of dissociation between PGE2 and Tyr release and of lack of proteolytic activity for IL-1.
Civelli
M
M
Institute of Pharmacological Sciences, Milan, Italy.
Agradi
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Bozzetti
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Letari
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Nicosia
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D000818:Animals; D002100:Cachexia / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism*; D009369:Neoplasms / Q000097:blood*; D010949:Plasma / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012132:Respiratory Muscles / Q000378:metabolism; D014443:Tyrosine / Q000097:blood
D007375:Interleukin-1; D009124:Muscle Proteins; D011994:Recombinant Proteins; D014443:Tyrosine; D015232:Dinoprostone