Restraint stress induces lymphocyte reduction through p53 and PI3K/NF-κB pathways

Restraint stress, either physical or psychological, can modulate immune function. However, the mechanisms associated with stress-induced lymphocyte reduction remains to be elucidated. We have previously shown that chronic stress induces Fas-mediated lymphocyte reduction. Here, we investigated the mechanisms by which restraint stress modulates lymphocyte reduction. Our data have shown that inhibition of p53 by the p53 inhibitor PFT-alpha attenuates stress-induced reduction in lymphocyte numbers. These results were verified using p53 knockout mice, suggesting a pivotal role of p53 in this process. In addition our data have indicated that PI3K/nuclear factor kappa B (NF-kappa B) signaling pathway plays an important role in the stress-induced lymphocyte reduction. Our study thus demonstrates that restraint stress promotes lymphocyte reduction through p53 and PI3K/NF-kappa B pathways. (c) 2008 Elsevier B.V. All rights reserved.