Abstract
We have investigated the secretion of interferon alpha (IFN-alpha), IFN-gamma, interleukin-1alpha (IL-1alpha), IL-1beta, IL-2 and tumour necrosis factor alpha (TNF-alpha) in whole blood cell cultures (WBCCs) of colorectal cancer patients upon mitogen stimulation. Whereas the values for IL-1beta and TNF-alpha remained virtually unchanged in comparison with healthy control subjects, WBCCs of colorectal cancer patients secreted significantly lower amounts of IFN-alpha (P < 0.005), IFN-gamma (P < 0.0001), IL-1alpha (P < 0.0001) and IL-2 (P < 0.05). This reduction correlated with the progression of the disease. The total leucocyte and monocyte population were almost identical in both groups. In contrast, a dramatic depletion of lymphocytes was observed in colorectal cancer patients, which affected both lymphocyte counts (P < 0.0005) and their distribution (P < 0.0001). Our results suggest a selective suppression of cytokines in colorectal cancer patients that is related to tumour burden. Several mechanisms might account for this phenomenon, one of which might be lymphocyte depletion.
Highlights
We first established the normal range of cytokine production in whole blood cell cultures (WBCCs) in a group of -4 healthy adults according to previously established protocols (Fischer et al 1995)
In the present study we demonstrate that WBCCs from colorectal cancer patients have an impaired capacity to secrete cytokines upon mitogen stimulation
Our results show that cytokine-secreting peripheral immune cells from colorectal cancer patients are not commonly suppressed as they display a virtually unchanged capacity to secrete IL-1 and tumour necrosis factor a (TNF-a). indicating that the suppression is selective
Summary
PatientsBlood samples were tak-en from -4 healthy x olunteers (mean age 52 years. range 29-62) and from 28 patients (17 male. 11 female) wxith histologicallv confirmed colorectal carcinoma (mean age 67 -ears. range 40-82). Blood samples were tak-en from -4 healthy x olunteers 11 female) wxith histologicallv confirmed colorectal carcinoma In 13 patients early stages w ere diacnosed (Dukes' A and B). Whereas 15 showxed progressed stages of colorectal carcinoma (Dukes' C and D). None of the patients had receixed chemoor radiotherapy before the time wxhen blood w as taken. The Newxcastle disease X irus (NDV) preparation xas kindly proxvided by Dr R Zawatzky
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