Leukocyte endogenous mediator fails to alter protein dynamics in a model of liver dysfunction.
This study examines the effect of a purified leukocyte-derived endogenous mediator (LEM) on protein metabolism during liver dysfunction and after sham surgery and the role of a nonsteroidal, antiinflammatory drug (indomethacin sodium trihydrate) in modifying this response. Febrile response, protein kinetics, urinary end products of protein metabolism, and plasma acute phase protein levels were studied in rats given a pyrogenic dose of LEM or saline solution, and these same indicators were studied after the administration of the same dose of LEM plus 2 mg/kg indomethacin 3 weeks after a portacaval shunt (PCS) or sham operation. In both surgical groups given LEM, a maximum of 1.1 degrees C fever was observed. LEM increased protein turnover and urinary excretion of nitrogen and urea in sham-operated rats but not in the PCS animals. Administration of indomethacin decreased the plasma oxidation of L[1-14C]leucine and prevented the increased excretion of total nitrogen and urea in sham-operated animals treated with LEM. PCS animals showed a constant excretion of nitrogen and urea independent of treatment. alpha 1-Acid glycoprotein levels increased significantly in sham-operated animals treated with LEM but not in the PCS group until indomethacin was added. The coadministration of LEM and indomethacin in shams also enhanced the levels of alpha 2-macroglobulin and alpha 1-acid glycoprotein over values found with LEM alone. These findings confirm the catabolic effect of LEM in normal animals and identify the essential role of the liver in the acute phase response. The data also suggest that indomethacin may modify the acute phase response by reducing plasma amino acid oxidation as well as enhancing the levels of some specific acute phase proteins.
Flores
E A
EA
Cancer Research Institute, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02215.
Drabik
M
M
Gauldie
J
J
Blackburn
G L
GL
Dinarello
C A
CA
Bistrian
B R
BR
D000209:Acute-Phase Proteins / Q000032:analysis; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D009584:Nitrogen / Q000378:metabolism; D011167:Portacaval Shunt, Surgical; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000209:Acute-Phase Proteins; D000596:Amino Acids; D007375:Interleukin-1; D011506:Proteins; C008270:leukocyte endogenous mediator; D009584:Nitrogen; D007213:Indomethacin