Pancreatic cancer as a model: inflammatory mediators, acute-phase response, and cancer cachexia.
Patients with pancreatic cancer frequently develop the syndrome of cancer cachexia. Pro-inflammatory cytokines have been strongly implicated in the pathogenesis of this syndrome. In patients with pancreatic cancer an acute-phase response (an index of pro-inflammatory cytokine activity) is associated with accelerated weight loss, hypermetabolism, anorexia, and a shortened duration of survival. However, little is known about the primary significance of the acute-phase response in terms of altered hepatic export protein synthesis rates and its potential impact on the body's nitrogen economy. In a recent series of studies on weight-losing pancreatic cancer patients with hypoalbuminemia we have demonstrated albumin synthesis to be unaltered whereas fibrinogen synthesis is increased two- to threefold compared with healthy controls. Because of the mismatch in amino acid composition between the body's main labile amino acid reserve (skeletal muscle) and that of acute-phase proteins, these results lend support to the concept that in pancreatic cancer the reprioritization of body protein metabolism during an acute-phase response may well be a significant factor in the loss of lean tissue in these patients.
Fearon
K C
KC
Department of Surgery, University of Edinburgh, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, UK.
Barber
M D
MD
Falconer
J S
JS
McMillan
D C
DC
Ross
J A
JA
Preston
T
T
D000209:Acute-Phase Proteins / Q000378:metabolism; D000210:Acute-Phase Reaction / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D000855:Anorexia / Q000209:etiology; D002100:Cachexia / Q000209:etiology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005340:Fibrinogen / Q000096:biosynthesis; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008659:Metabolic Diseases / Q000209:etiology; D018482:Muscle, Skeletal / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000150:complications / Q000378:metabolism*; D014176:Protein Biosynthesis; D012709:Serum Albumin / Q000096:biosynthesis / Q000378:metabolism; D015996:Survival Rate; D015431:Weight Loss
D000209:Acute-Phase Proteins; D000596:Amino Acids; D016207:Cytokines; D018836:Inflammation Mediators; D012709:Serum Albumin; D005340:Fibrinogen; D009584:Nitrogen