Insights on neuroendocrine regulation of immune mediators in female reproductive aging and cancer

Abstract

Neuroendocrine-immune homeostasis in health and disease is a tightly regulated bidirectional network that influences predisposition, onset and progression of age-associated disorders. The complexity of interactions among the nervous, endocrine and immune systems necessitates a complete review of all the likely mechanisms by which each individual system can alter neuroendocrine-immune homeostasis and influence the outcome in age and disease. Dysfunctions in this network with age or external/internal stimuli are implicated in the development of several disorders including autoimmunity and cancer. The existence of sympathetic noradrenergic innervations on lymphoid organs in synaptic association with immune cells that express receptors for endocrine mediators such as hormones, neural mediators such as neurotransmitters and immune effector molecules such as cytokines explains the complicated nature of the regulatory pathways that must always maintain homeostatic equilibrium within and among the nervous, endocrine and immune systems. The incidence, development and progression of cancer, affects each of the three systems by disrupting regulatory pathways and tipping the scales away from homeostasis to favour pathways that enable it to evade, override and thrive by using the network to its advantage. In this review, we have explained how the neuroendocrine-immune network is altered in female reproductive aging and cancer, and how these modulations contribute to incidence and progression of cancer and hence prove to be valuable targets from a therapeutic standpoint. Reproductive aging, stress-associated central pathways, sympathetic immunomodulation in the periphery, inflammatory and immunomodulatory changes in central, peripheral and tumor-microenvironment, and neuro-neoplastic associations are all likely candidates that influence the onset, incidence and progression of cancer.

Keywords

• neuroimmunology
• cytokines
• tumor microenvironment
• neuro-neoplastic associations
• norepinephrine
• sympathetic innervation