Essential Role of IL-10/STAT3 in Chronic Stress-Induced Immune Suppression
Document Type
Article
Publication Date
1-1-2014
Description
Stress can either enhance or suppress immune functions depending on a variety of factors such as duration of stressful condition. Chronic stress has been demonstrated to exert a significant suppressive effect on immune function. However, the mechanisms responsible for this phenomenon remain to be elucidated. Here, male C57BL/6 mice were placed in a 50-ml conical centrifuge tube with multiple punctures to establish a chronic restraint stress model. Serum IL-10 levels, IL-10 production by the splenocytes, and activation of STAT3 in the mouse spleen were assessed. We demonstrate that IL-10/STAT3 axis was remarkably activated following chronic stress. Moreover, TLR4 and p38 MAPK play a pivotal role in the activation of IL-10/STAT3 signaling cascade. Interestingly, blocking antibody against IL-10 receptor and inhibition of STAT3 by STAT3 inhibitor S3I-201 attenuates stress-induced lymphocyte apoptosis. Inhibition of IL-10/STAT3 dramatically inhibits stress-induced reduction in IL-12 production. Furthermore, disequilibrium of Th1/Th2 cytokine balance caused by chronic stress was also rescued by blocking IL-10/STAT3 axis. These results yield insight into a new mechanism by which chronic stress regulates immune functions. IL-10/STAT3 pathway provides a novel relevant target for the manipulation of chronic stress-induced immune suppression.
Citation Information
Hu, Dan; Wan, Lei; Chen, Michael; Caudle, Yi; LeSage, Gene; Li, Qinchuan; and Yin, Deling. 2014. Essential Role of IL-10/STAT3 in Chronic Stress-Induced Immune Suppression. Brain, Behavior, and Immunity. Vol.36 118-127. https://doi.org/10.1016/j.bbi.2013.10.016 PMID: 24513872 ISSN: 0889-1591