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Background: Epinephrine is one of the major hormones orchestrating numerous physiological responses of the organism exposed to acute or chronic stress. In those cases the plasma level of the hormone exceeds manifold the physiological values present in healthy resting individuals. Higher epinephrine concentrations affect the immune system and modulate macrophages immune responses. The purpose of the present work was to detect if physiological concentrations of epinephrine may alter the capacity of human peripheral blood mononuclear cells (PBMC) for cytokine production, without and following co-incubation with HT-29 cells from a human colon cancer cell line. Methods: PBMC were incubated for 24 hours with the following concentrations of epinephrine-0.025 ng/ml, 0.05 ng/ ml and 0.1 ng/ml added at 10 μl/ml culture medium. The secretion of TNFα, IL-1β, IL-6, IFNγ, IL-10, and IL-2 was detected using the ELISA method. In another set of experiments the production of the same cytokines was assessed following co-incubation of PBMC with HT-29 cells. Results: 24 hrs of incubation with epinephrine had no effect on PBMC proliferation rate, whereas that of HT-29 colon cancer cells was significantly reduced. While epinephrine caused increased secretion of IL-6 by non-stimulated PBMC, the production of TNFα, IL-1β, IFNγ, and IL-10 was not affected. Epinephrine exerted no effect on TNFα, IL-1β, IL-6 and IL-10 production induced by LPS and on the release of IL-2 by PBMC activated with PMA. However the production of IFNγ by PBMC stimulated with PMA was increased. The secretion of pro-inflammatory cytokines hereby tested by HT-29-stimulated PBMC was not affected upon incubation with epinephrine. On the other hand, IL-10 secretion by HT-29 stimulated PBMC was slightly reduced. Conclusions: While small, physiological doses of epinephrine slightly stimulated PBMC for IL-6 and IL-10 production, it appears that the capacity of the mononuclear cells for massive cytokine release could be stirred only with extensive amounts of hormone, even higher than those freed during acute and chronic stress as studies have indicated. Small doses of epinephrine do not alter the immune cross talk between PBMC and HT-29 colon cancer cells.

Do Physiological Doses of Epinephrine May Act as Immunomodulator and Mediator between Immune and Colon Cancer Cells?