On the Immune Relationship Between Urea, Human Mononuclears and Colon Cancer Cells

Background: Increased serum urea level is an early herald of chronic renal failure. Inflammatory cytokines produced by Peripheral Blood Mononuclear Cells (PBMC) upon the effect of urea and other toxins initiate and maintain inflammation that persist and converts to a chronic state. Since chronic inflammation is a predisposing factor for carcinogenesis it was the aim of the study to examine the effect of urea on the immune dialogue between PBMC and human colon cancer cells from two lines (HT-29 and RKO). Methods: Cytokine production by non-stimulated human PBMC or cells stimulated with either mitogen or with HT-29 and RKO colon cancer cells were incubated for 24 hrs with various concentrations of urea (40-200 mg/dl) and the secretion of TNFα, IL-1β, IL-6, IFNγ, IL-2, IL-10 and IL-1ra, was determined by ELISA. Results: Urea caused increased secretion of the pro-inflammatory cytokines TNFα, IL-1β, IFNγ and the anti-inflammatory cytokine IL-10 by non-stimulated PBMC and enhanced production of IFNγ by PMA/ionomycin stimulated cells. In addition, the secretion of TNFα, IFNγ and IL-2 induced by RKO colon cancer cells was elevated following 24 hrs of incubation with urea, whereas the synthesis of IL-1β induced by HT-29 cells was reduced. Conclusion: Although the results indicate that urea may exert a certain concentrationand cell dependent effect on the immune equilibrium between PBMC and colon cancer cells, the impaired immunity observed in patients with chronic renal failure cannot be the principal promoter for increased cancer risk reported in those individuals.