Bidirectional communication between the neuroendocrine system and the immune system: relevance to health and diseases

Abstract

In the past century, physiological, molecular, and cellular-based studies have proved that the functions of the nervous system, endocrine system, and immune system are dependent upon each other and that this interaction among these systems determines the maintenance of health or susceptibility to infections. The release of neurotransmitters and neuropeptides from the brain is a response to external environmental stimuli that influences the release of hormones from the pituitary in order to regulate the functions such as metabolism and growth, reproduction, etc. In addition, there are direct sympathetic noradrenergic and peptidergic innervations of primary (bone marrow and thymus) and secondary (spleen, lymph nodes, and lymphoid tissues) lymphoid organs. The neurotransmitters and neuropeptides released in these lymphoid organs then bind to specific receptors on the cells of the immune system to modulate their functions. Another circuit in this bidirectional communication involves the products of the immune system, for e.g., cytokines that can cross the blood-brain barrier to alter the activities of the neuronal function in the central nervous system especially during fever and inflammation in infectious diseases and cancer. Dysregulation of the interactions between the neuroendocrine and immune system due to alterations in the neural activity, secretion of hormones and cytokines, and synthesis of growth factors has been demonstrated to promote the pathogenesis and progression of infectious and autoimmune diseases, cancer, and neurodegenerative diseases. It is imperative that further research is carried out to understand the mechanisms of neuroendocrine-immune interactions to facilitate development of better treatment strategies for neurodegenerative diseases.

Keywords: Brain; Cytokine; Hormone; Lymphoid organs; Neurotransmitter.

Fig. 1:

Bidirectional communication between the neuroendocrine system and immune system.

1. The bidirectional interaction is mainly through neurotransmitter-, hormonal-, and cytokine-specific pathways. The CNS influences the immune system via neuroendocrine outflow, and autonomic and sensory nerves that innervate lymphoid tissue. Peripherally, cytokines produced by the immune cells under the influence of neuronal activity cross the blood-brain barrier to influence CNS functions. There is a great complexity in neural-immune interactions.

2. Neurotransmitter-specific and neuropeptidergic nerves are distributed in the rostral sections of the brain arising from the cell bodies located in the caudal portions of the brain. The neuroglial cells, astrocytes and microglia, regulate the neuronal survival through the release of cytokines and growth factors while the oligodendrocytes are critical to myelin formation. The neuroendocrine systems in the hypothalamus control metabolism and growth by influencing the release of hormones from the pituitary.

3. Noradrenergic nerves originate from ganglia and are distributed to specific lymphoid compartments in lymphoid organs and the effects are mediated through the receptors for neurotransmitters on the cells of the immune system. The presence of β2-adrenergic receptors (AR) on the subpopulations of lymphoid cells facilitates the binding of norepinephrine (NE) to alter the release of cytokines, growth factors, and immune molecules that cross the blood-brain barrier to alter brain functions.