Metabolic disturbance and sensitivity to endotoxin in patients with advanced cancer: relationship to lymphocyte reactivity, tumour necrosis factor (TNF) production and survival.

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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.)