Pro-inflammatory cytokine release by peripheral blood mononuclear cells from patients with advanced pancreatic cancer: relationship to acute phase response and survival.
The acute phase protein response (APPR) and peripheral blood mononuclear cell-derived inflammatory cytokine production was assessed in patients with advanced pancreatic cancer and age-matched healthy volunteers. We examined the relationship between the APPR, cytokine production and survival in these patients. Forty-two patients with pancreatic cancer cachexia and twelve age-matched healthy controls were recruited. The nutritional status, Karnofsky performance score, C reactive protein (CRP), serum interleukin-6, and in vitro monocyte interleukin-1 and interleukin-6 production were measured. The dates of death of the pancreatic cancer patients were subsequently obtained and appropriate patient variables at baseline were entered into a Cox's proportional hazards model. The cancer patients had significantly lower: body mass index, Karnofsky performance score, serum albumin and elevated CRP and stimulated interleukin-6 production. Both univariate and multivariate analysis demonstrated a strong association between tumour stage, CRP, stimulated interleukin-6 production and survival. Monocytes in cachectic pancreatic cancer patients are primed to produce high levels of interleukin-6 when stimulated. Overproduction of interleukin-6 has a negative impact on survival. Decreased survival is associated with an elevated APPR. While the elevated APPR is probably related to locally produced interleukin-6 in the liver, it seems possible that locally and systemically produced interleukin-6 influences survival.
Moses
Alastair G W
AG
Department of Clinical and Surgical Sciences (Surgery), University of Edinburgh, Royal Infirmary, Edinburgh, EH16 4SA, UK.
Maingay
Jean
J
Sangster
Kathryn
K
Fearon
Kenneth C H
KC
Ross
James A
JA
D000210:Acute-Phase Reaction; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000097:blood*; D015118:Eicosapentaenoic Acid / Q000097:blood; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000401:mortality
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D002097:C-Reactive Protein; D015118:Eicosapentaenoic Acid