Cytokines: Sensors of the nervous system

Abstract

The central nervous system (CNS) and the immune system share multiple chemical messengers ranging from small molecules, such as corticotropin-releasing factor (CRF) to large proteins, such as cytokines and growth factors. The immune system is capable of sending signals to the brain through an elaborate system of bi-directional communication. These signals induce responses to the damage caused by viruses, bacteria, parasites and molecules, such as the damage associated molecular pattern molecules (DAMP). The blood-brain barrier prevents the entry of antibodies, complement factors, immune cells and cytokines into the interior of brain parenchyma. Notably, cells of the CNS lack CCR5, B cells, dendritic cells and activated macrophages in a homeostatic state. This organization diminishes immune responses in the brain. It has now been demonstrated that CNS is permanently under the control and surveillance of activated macrophages and dendritic cells, as well as Th cells that are located in the meninges and choroid plexus. These strategic areas can safeguard ventricular and subarachnoid compartments. There are multiple anatomo-physiological connections between the CNS, immune system and autonomous nervous system (ANS) via the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary axis (SAM). Cytokines are mediators of intra-and extracellular communications which serve as powerful regulators of neuropeptidergic systems. They maintain neuroendocrine homeostasis, and are involved in responses to stress and depression. Chemokines and prostaglandins (PGs) are essential to generate a powerful response from the immune system. Some of the cytokines involved include TNF-α, IL-1ß, IL-4, IL-6, IL-10, IL-12, IL-15, IL-19, IL-18, IL-33 and interferon type I (IFN-β and IFN-α) and type-II (IFN-γ). These molecules act as potent modulators of responses in the neuroendocrine system. In this chapter we review interactions between the immune system and nervous system. © 2012 by Nova Science Publishers, Inc. All rights reserved.