Stress induced neuroendocrine-immune plasticity

Abstract

Research over the past decade has revealed close interaction between the nervous and immune systems in regulation of peripheral inflammation linking psychosocial stress with chronic somatic disease and aging. Moreover emerging data suggests that chronic inflammations lead to a pro-inflammatory status underlying premature aging called inflammaging. In this context, the spleen can be seen as a switch board monitoring peripherally derived neuroendocrine-immune mediators in the blood and keeping up a close communication with the central stress response via its mainly sympathetic innervation. The effect aims at balanced and well-timed stress axis activation and immune adaptation in acute peripheral inflammatory events. Constant adjustment to the needs generated by environmental and endogenous challenges is provided by neuroendocrine-immune plasticity. However, maladaptive plasticity induced e.g., by chronic stress-axis activation and excessive non-neuronal derived neuroendocrine mediators may be at the heart of the observed stress sensitivity promote inflammaging under chronic inflammatory conditions. We here review the role of neurotransmitters, neuropeptides and neurotrophins as stress mediators modulating the immune response in the spleen and their potential role in inflammaging.

Connexin 43 in splenic lymphocytes is involved in the regulation of CD4+CD25+ T lymphocyte proliferation and cytokine production in hypertensive inflammation

“…As a secondary lymphoid organ and a source of vasoactive factors, the spleen controls the amount of peripheral neuroendocrine and immune mediators in the blood, and maintains a close interaction with the central system via sympathetic innervation in response to stress ( 26 , 27 ). Spleen removal can induce hypertension and lead to tissue injury.…”

Monocyte trafficking to the brain with stress and inflammation: a novel axis of immune-to-brain communication that influences mood and behavior

“…These monocytes are termed “inflammatory” because they are able to traffic throughout the body and have enhanced capacity to release pro-inflammatory cytokines upon entering tissue and becoming effector cells. This is relevant because stress-induced trafficking of inflammatory monocytes contributes to the exacerbation of both mental and physical health conditions (Dutta et al, 2012 ; Hanke et al, 2012 ; Liezmann et al, 2012 ; Seifert et al, 2012 ; Wohleb et al, 2013 , 2014a ; Heidt et al, 2014 ).…”

Altered Neuroendocrine Immune Responses, a Two-Sword Weapon against Traumatic Inflammation

“…Meanwhile, many other cells including endothelial cells in brain ventricle, microglia, and atrocities can also release multiple immunomodulatory elements of the central nervous system (CNS). Also, the neuronal and endocrinal cells may receive immune signals via their corresponding immune-related receptors (cytokine receptors, pattern recognition receptors, chemokine receptors, nuclear receptors) 37 - 43 . Concurrently, the immunocytes release various cytokines (lymphokines, monokines, etc.)…”

“…Concurrently, the immunocytes release various cytokines (lymphokines, monokines, etc.) to affect the neuroendocrine responses as well as sensing the local or distant stressful signals 43 - 45 termed “flowing brain”. The sharing of ligands and receptors allows the immune system to serve as the sixth sense notifying the nervous system of the presence of foreign entities 46 .…”