Dysregulated immune system in chronic stress male rats is an outcome of altered mRNA expression, cytokines, and Th1/Th2 balance.

Chronic stress is known to cause immune system dysfunction, which can contribute to the development of various highly prevalent diseases. Nevertheless, the mechanisms underlying immune dysregulation during chronic stress remain poorly understood. In this study, we examined the effects of 35-day chronic unpredictable mild stress (CUMS) on behavioral patterns, lymphocyte subpopulation ratios, serum cytokine levels, and the peripheral blood leukocyte transcriptome in 20 male Sprague-Dawley rats. After 35 days of CUMS exposure, the rats exhibited established features of chronic unpredictable mild stress, including increased anxiety-like behavior and depression-like behavior. We found a significant increase in the proportion of Th2 cells among lymphocytes, leading to a Th1/Th2 imbalance. Additionally, serum levels of the pro-inflammatory cytokines IL-1α, IL-1β, IFN-γ, and GM-CSF were significantly decreased, whereas the concentration of IL-2 was markedly elevated. Transcriptomic profiling revealed broad alterations in gene expression after CUMS, particularly in pathways related to immune system function. Our findings indicate that chronic stress induces immune dysregulation through a Th1/Th2 imbalance and associated changes in key immune-related genes (including Maf, Irf4, Gfi1, and Bcl6b), suggesting a potential mechanism for stress-induced immune dysfunction.