Chronic Stress and IL-10/STAT3 Pathway’s Induction

Chronic Stress and IL-10/STAT3 Pathway’s Induction

A study published in Brain, Behavior, and Immunity journal indicates that the interleukin (IL)-10/STAT3 pathway may play a key role in the immunosuppression induced by chronic stress.

IL-10 is a major anti-inflammatory cytokine, which possesses potent immunosuppressive actions. Stress mediators, particularly catecholamines (CAs), are potent IL-10 inducers, and in clinical conditions such as brain trauma, the massive CAs-induced IL-10 release has been linked to severe immunosuppression (IJ Elenkov et al., Proc Assoc Am Physicians, 1996, 108:374; F Ramírez F et al., J Immunol, 1996, 156:2406; C Woiciechowsky et al., Nat Med, 1998, 4:808). It is also known that STAT3, a key member of the Stat family, can be activated by IL-10 signaling, and IL-10R appears unique in promoting a potent anti-inflammatory response via STAT3 induction (El Kasmi et al., J Immunol, 2006, 177:7880).

In this study, Dan Hu and colleagues from the East Tennessee State University, Johnson City, TN, US and the Wuhan University, Wuhan, China measured serum IL-10 levels, IL-10 production by splenocytes, and activation of splenic STAT3 in mice that have been subjected to chronic physical restraint stress.

The authors demonstrated that the IL-10/STAT3 axis is activated by the TLR4/p38 pathway following chronic stress. Furthermore, evidence was obtained that the IL-10/STAT3 pathway may also be involved in triggering lymphocyte apoptosis, the suppression of IL-12 production, and the induction of a T helper (Th)2 shift.

The study provides new insights into the mechanisms driving stress-induced immunosuppression and may suggest new therapeutic strategies along these lines.

Source: Brain Behav Immun. 2014, 36:118.

Read more: sciencedirect.com

Source: Crystal structure of IL-10 and IL-10R signaling. Credit: Wikimedia Commons, http://en.wikipedia.org/wiki/Interleukin_10 and sinobiological.com http://old.sinobiological.com/Interleukin-10-Interferon-Family-Protein-Antibody-a-284.html Public domain.

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