Neurohormonal-cytokine interactions: Implications for inflammation, common human diseases and well-being

https://doi.org/10.1016/j.neuint.2007.06.037Get rights and content

Abstract

The neuroendocrine system affects the immune system through the neuroendocrine humoral outflow via the pituitary, and through direct neuronal influences via the sympathetic, parasympathetic (cholinergic) and peptidergic/sensory innervation of peripheral tissues. Circulating hormones or locally released neurotransmitters and neuropeptides regulate major immune functions, such as antigen presentation, antibody production, lymphocyte activity, proliferation and traffic, and the secretion of cytokines including the selection of T helper (Th)1 or Th2 cytokine responses. During inflammation, the activation of the stress system, through induction of a Th2 shift protects the organism from systemic “overshooting” with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones, substance P, ATP and the activation of the corticotropin-releasing hormone/substance P-histamine axis may actually facilitate inflammation, through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor (TNF)-α and CRP production. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the ‘systemic anti-inflammatory feedback’ and/or ‘hyperactivity’ of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression and atherosclerosis. Better understanding of the neuroendocrine control of inflammation may provide critical insights into mechanisms underlying a variety of common human immune-related diseases.

Section snippets

Cytokines and allergy/atopy

Allergic diseases, such as asthma, seasonal and perennial allergic rhinitis, eczema and IgE-mediated food allergy, are characterized by dominant Th2 responses, overproduction of histamine and a shift to IgE production (Humbert et al., 1999, Wills-Karp, 2001). The Th2 cytokines IL-4 and IL-13 induce B lymphocytes to express the ɛ-germeline gene transcript, an essential precursor for immunoglobulin heavy chain rearrangement and IgE antibody (Ab) production. IL-5 is selective for eosinophils (Eo)

Neurohormonal regulation of cytokine production

The brain affects the immune system through the neuroendocrine humoral outflow via the pituitary, and through direct neuronal influences via the sympathetic, parasympathetic (cholinergic) and peptidergic/sensory innervation of peripheral tissues including lymphoid organs and blood vessels (Fig. 1). Cytokine regulation is traditionally linked to the effects of immuno-genetic factors operating exclusively within the immune system. Evidence accumulated over the last 2–3 decades indicates, however,

Implications for inflammation, common human diseases and well-being

Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis, health and well-being. The inflammatory reaction, like the stress response is crucial for survival of the self and species. Also, like the stress response, inflammation is meant to be tailored to the stimulus and time-limited. A fully fledged systemic inflammatory reaction results in stimulation of four major programs: (1) the acute phase reaction, (2) the sickness syndrome, (3) the

Conclusions

The CNS and the immune system are the two major adaptive systems of the body (Elenkov et al., 2000). Inflammation, and particularly chronic inflammation of varying types, as a result of the failure of these two major adaptive systems to respond and resolve it, affect the well-being of the individual, including behavioral parameters, such as cognitive ability, performance, affect and sleep, as well as indices of metabolic and cardiovascular health that are known to influence human life

Acknowledgement

This work was supported by a Marie Curie International Reintegration Grant (I.J.E.) within the 6th European Community Framework Program.

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