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J Neuroimmunol. 2008 Feb;194(1-2):115-22. doi: 10.1016/j.jneuroim.2007.12.002. Epub 2008 Jan 14.

Toll-like receptor 4 mediates chronic restraint stress-induced immune suppression.

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  • 1Departments of Internal Medicine, James Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.


Stress, either physical or psychological, can have a dramatic impact on the immune system. Little progress, however, has been made in understanding stress-induced immune suppression. We report here that mice subjected to chronic 12-hour daily physical restraint for two days significantly increased the expression of Toll-like receptor 4 (TLR4). Interestingly, TLR4-deficient mice are resistant to stress-induced lymphocyte reduction. In addition, restraint stress caused dramatic decrease in T help 1 (Th1) cytokine IFN-gamma and IL-2 levels but increase in Th2 cytokine IL-4 in wild type mice. Moreover, the restraint stress significantly inhibits changes of Th1 and Th2 cytokines in TLR4-deficient mice compared with the wild type mice. Therefore, stress modulates the immune system through a TLR4-dependent mechanism.

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