Abstract <p>In recent years, the role of the immune system in the implementationof the stress response has been in the focus of neurobiologicalresearch. Chronic stress is often associated with cytokine imbalanceand the development of a persistent inflammatory response. The aimof this study was to investigate the effect of lipopolysaccharide(LPS) on blood cytokine levels in rats exposed to chronic unpredictablemild stress (CUMS). The study was carried out on 90 male Wistarrats, were exposed to CUMS for 1–4 weeks, while being preadministeredeither LPS (experiment) or physiological saline (control). The serum concentrationsof TNF-α, IL-4, and IL-10 were determined by ELISA. After the firstweek of CUMS modeling, LPS-preadministered animals showed a statisticallysignificant increase in IL-10 and TNF-α levels, whereas CUMS exposurealone was not accompanied by changes in the studied cytokines. After twoweeks of stress exposure, IL-10 and TNF-α levels were increasedboth in the experiment and in the control. After three weeks ofnegative emotiogenic loads, TNF-α level was elevated only with CUMS exposurealone. After four weeks of stress exposure, no statistically significantchanges in IL-4, IL-10, and TNF-α levels were observed in any ofthe experimental groups compared to intact rats. Thus, LPS preadministrationleads to the activation of immune responses at early stages of CUMSmodeling, whereas at later stages, a prior antigenic exposure doesnot affect stress-induced changes in the concentration of the studiedcytokines. The obtained data are promising in terms of developingnew methods and approaches for the prevention or correction of immune-dependentstress-induced disorders.</p>