Reduction in cytokine production in colorectal cancer patients: association with stage and reversal by resection

The aim of this study was to assess monocyte/macrophage function, as define d by lipopolysaccharide (LPS)-induced production of tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and interferon (IFN)-gamma by stimulated w hole blood cultures in patients with colorectal carcinoma before and after surgical resection, Forty colorectal cancer patients prior to surgery and 3 1 healthy controls were studied. Heparinized venous blood was taken from co lorectal cancer patients prior to surgery and from healthy controls. Serial samples were obtained at least 3-6 weeks post-operatively Blood was stimul ated with LPS for 24 h and supernatants were assayed for TNF-alpha, IFN-gam ma and IL-10 by enzyme-linked immunosorbent assay. LPS-induced production o f TNF-alpha and of IFN-gamma was reduced in patients with colorectal carcin oma compared to controls (TNF-alpha, 11 269 pg ml(-1) {12 598}; IFN-gamma, 0.00 pg ml(-1) {1226}, median {IQR}) (TNF-alpha, 20 576 pg ml(-1) {11 637}, P < 0.0001; IFN-gamma, 1048 {2428}, P = 0,0051, Mann-Whitney U-test), Prod uction in patients after surgery had increased (TNF-alpha, 17 620 pg ml(-1) {7986}; IFN-gamma: 410 pg ml(-1) (2696); mean {s.d.} and were no longer si gnificantly reduced when compared to controls (TNF-alpha, P = 0.28; IFN-gam ma P = 0.76). Production of TNF-alpha and IFN-gamma prior to surgery were r educed to a greater extent in patients with Dukes' stage C tumours compared to those with Dukes' stage A and B stage. There was no difference in IL-10 production between any group. Monocytes/macrophages from patients with col orectal carcinoma are refractory to LPS stimulation as reflected by reducti on in TNF-alpha and IFN-gamma production and this is more pronounced in pat ients with advanced stage tumours. This suppression is not mediated by IL-1 0 and disappears following surgical resection of the tumour. This provides evidence for tumour induced suppression of immune function in patients with colorectal cancer and identifies a potential therapeutic avenue. (C) 2000 Cancer Research Campaign.