title: Metabolic disturbance and sensitivity to endotoxin in patients with advanced cancer: relationship to lymphocyte reactivity, tumour necrosis factor (TNF) production and survival.
abstract: Increased TNF production and impaired lymphocyte function have been individually linked with metabolic disturbance, endotoxaemia and mortality in humans. The inter-relationship between these observations was investigated in humans with cancer. In 13 patients with metastatic colorectal cancer and seven healthy volunteers, observations (n = 23) included peripheral blood mononuclear cell (PBMC) TNF production, IL-2 production and phytohaemagglutinin (PHA) response; the acute-phase protein response (APPR) (serum C-reactive protein (CRP), albumin, CRP/albumin ratio), and survival. APPR correlated with survival (CRP, r = -0.689, P = 0.006; CRP/albumin, r = -0.758, P = 0.002; albumin, r = 0.655, P = 0.011), but not with TNF production. TNF production in response to in vitro endotoxin correlated with impaired lymphocyte function in patients (r = 0.567, P = 0.043) and in the whole group (r = 0.65, P = 0.001). The ratio (basal PBMC TNF production)/(lymphocyte function) correlated with CRP (r = 0.569, P = 0.042), CRP/albumin (r = 0.617, P = 0.025), endotoxin sensitivity (r = 0.567, P = 0.043) and survival (r = -0.545, P = 0.038) in patients, and the whole group (P < 0.002). Impaired lymphocyte function may influence TNF production, endotoxin sensitivity and metabolic disturbance in humans with cancer. (r = Spearman correlation coefficient.)
authors.affiliation: Department of Surgery, University of Aberdeen Medical School, UK.
authors.forename: D B
authors.initials: DB
authors.lastname: Gough
authors.forename: K C
authors.initials: KC
authors.lastname: Fearon
authors.forename: D C
authors.initials: DC
authors.lastname: Carter
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D004731:Endotoxins / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000556:secondary; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000032:analysis; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015431:Weight Loss
chemical_list: D004731:Endotoxins; D007376:Interleukin-2; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein