Changes in Cytokine Profile of Macrophages Induced by Chronic Stress in intact and tumor-bearing rats

Abstract

Background. The prolonged psychoemotional stress results in the individual adaptive response ensured by the coor- dinated interactions among the nervous, endocrine, and immune systems. A key role in this process is played by the interaction between stress hormones and effector cells of innate immunity, particularly macrophages (Mph), which con- stitute the first line of host defense. The aim of this study was to experimentally investigate the effects of stress hormones on the cytokine spectrum produced by Mph of the intact and tumor-bearing rats. Materials and Methods. Wistar rats with transplanted Guerin carcinoma were used in a study. to induce experimental chronic stress, animals received dexamethasone or adrenaline (0.5 mg/kg body weight). Plasma levels of tNf-α, IL-6, and IL-10 were determined using ELISA. Results. In the intact animals, prolonged exposure to stress hormones resulted in significant alterations in the macrophage cytokine profile. Adrenaline administration was accompanied by a transient increase in tNf-α (p < 0.05) along with a simultaneous decrease in IL-10 (p < 0.05); subsequently, tNf-α production was suppressed against a marked increase in IL-10 synthesis. Dexamethasone induced an increased tNf-α production at later time points. In rats bearing Guerin carcinoma, the most pronounced changes in tNf-α and IL-10 production were observed following dexamethasone administration: on day 14, tNf-α levels significantly increased, followed by a sharp decline accompa- nied by the elevated IL-10 levels, reflecting Mph polarization from the M1 to the M2 phenotype. This indicates the deve- lopment of immunosuppression and correlates with the active tumor growth. A significant increase in IL-6 production was observed on day 14 under both adrenaline and dexamethasone exposure. Subsequently, adrenaline suppressed IL-6 production, whereas dexamethasone stimulated it, which may indicate the development of glucocorticoid resistance and paradoxical enhancement of inflammation. Conclusion. The prolonged exposure to stress hormones may create condi- tions favorable for tumor progression through suppression of innate immune effectors and development of immunosup- pression, as well as through paradoxical enhancement of inflammatory responses.