Peripheral blood cells from weight-losing cancer patients control the hepatic acute phase response by a primarily interleukin-6 dependent mechanism.
Cancer cachexia is associated with an elevated hepatic acute phase protein response, poor outcome and elevated cytokine production from peripheral blood mononuclear cells (PBMC). This study investigates the mechanism by which PBMC can induce a hepatic acute phase response. Supernatants from the peripheral blood cells of cancer patients induced significantly higher C-reactive protein (CRP) from hepatocytes (198+/-21 ng ml-1) than did supernatants from healthy controls (64+/-20, p<0.005). CRP production in vitro correlated with IL-6 production by PBMC from patients with pancreatic cancer (r=0.76, p<0.0001). This C-reactive protein production was reduced by 84% using neutralising antibody to IL-6 (p<0.001). There was a significant negative correlation between PBMC-induced hepatocyte C-reactive protein production and survival (r=-0.45, p<0.01). PBMC from cancer patients induce the hepatic acute phase response via a primarily IL-6-dependent mechanism.
O'Riordain
M G
MG
University Department of Surgery, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, UK.
Falconer
J S
JS
Maingay
J
J
Fearon
K C
KC
Ross
J A
JA
D000210:Acute-Phase Reaction / Q000276:immunology*; D000230:Adenocarcinoma / Q000276:immunology* / Q000401:mortality; D000368:Aged; D002097:C-Reactive Protein / Q000096:biosynthesis; D002100:Cachexia / Q000276:immunology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000401:mortality; D011228:Prealbumin / Q000096:biosynthesis; D015996:Survival Rate
D017077:Culture Media, Conditioned; D015850:Interleukin-6; D011228:Prealbumin; D002097:C-Reactive Protein