Hypothalamic-pituitary-adrenal axis cytokines

Keywords Alpha-melanocyte stimulating hormone Adre-nocorticotrophic hormone Corticotropin releasing hormone Cytokines Depression Hypothalamic-pituitary-adrenal axis Proenkephalin Proopiomelanocortin Schizophrenia Stress response... 

Turnbull AV, Rivier CL. Regulation of the hypothalamic-pituitary-adrenal axis by cytokines Actions and mechanisms of action. Physiol Rev 1999 79 1-79. 

IL-6 acts on the pituitary to induce adrenocorticotropic hormone (ACTH) release and directly on the adrenal glands to produce glucocorticoids. It is known that different cytoldnes that share gpl30 as a receptor subunit induce serum amyloid A, and potentiate the induction of IL-6 and the activation of the hypothalamic-pituitary-adrenal axis by IL-1. In particular, LIF, OSM, IL-11, and cardiotrophin-1 potentiate the elevation of serum corticosterone and IL-6 levels induced by IL-1. Furthermore, the potentiation of IL-1-induced serum corticosterone levels is not a consequence of the increased serum IL-6 observed after IL-1 administration. Thus either endogenous IL-6 does not mediate IL-l-induced corticosterone increase, or its role may be fulfilled by other cytokines. This is very important in the understanding of the activation of the hypothalamic-pituitary-adrenal axis and that potentiation of acute phase protein synthesis may represent an important feedback regulatory mechanism of inflammation. ... 

It has been shown that several monocyte-derived cytokines can act on the hypothalamic-pituitary-adrenal axis, stimulating adrenal cells to release corticosteroid hormones (B31, N2). Injection of IL-6 into rats results in an increase in concentrations of ACTH in the plasma (N2). IL-6 can also act directly on adrenal cells to induce corticosteroid release (S4, S5). IL-6 interacts with a number of cytokines to enhance the growth and differentiation of multipotent progenitor, erythroid, myeloid, and megakaryocytic cells (RIO, Rll, S60). 

This, in turn, has led to investigation of OP-mediated suppression of the hypothalamic-pituitary-adrenal axis (Pena-Philippides et al., 2007). However, anti-ChEs were also found to initiate acute immune responses. For example, the nerve agent soman induces an increase in the pro-inflammatory cytokine TNFa, IL-lp, and fL-6 in rats, including in the brain, where IL-lp is thought to contribute to irreversible brain damage (Banks and Lein, 2012). This bidirectional impairment of immune functions may reflect systemic responses that affect more than the cholinergic system alone. 

The sympathetic nervous system (SNS) and the hypothalamic-pituitary axis work together as important modulators of the immune system after exposure to stressors. Norepinephrine (NE) and epinephrine (EPI) (catecholamines from the SNS) and neuroendocrine hormones modulate a range of immune cell activities, including cell proliferation, cytokine and antibody production, lytic activity, and migration. This chapter will focus on these two major pathways of brain-immune signaling, briefly summarizing the evidence for SNS and hypothalamic-pituitary-adrenal (HPA) modulation of immune function, their influence on immune-mediated diseases, immune modulation in aging, and early life influences on these pathways. 

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