The immune system as the sixth sense

Abstract

Abstract. Blalock JE (University of Alabama, Birmingham, USA). The immune system as the sixth sense (Minisymposium). J Intern Med 2005; 257: 126-138.One of the truly remarkable discoveries in modern biology is the finding that the nervous system and immune system use a common chemical language for intra-and inter-system communication. This review will discuss some of the pivotal results that deciphered this chemical language. Specifically the nervous and immune systems produce a common set of peptide and nonpeptide neurotransmitters and cytokines that act on a common repertoire of receptors in the two systems. The paper will also review more recent studies that have delineated hardwired and humoral pathways for such bidirectional communication. This is discussed in the context of the idea that the sharing of ligands and receptors allows the immune system to serve as the sixth sense that notifies the nervous system of the presence of entities, such as viruses and bacteria, that are imperceptible to the classic senses. Lastly, this review will suggest ways to apply the newfound knowledge of the sixth sense to understand a placebo effect and to treate human disease.

Tuning immune tolerance with vasoactive intestinal peptide: A new therapeutic approach for immune disorders

“…Acting as a "sixth sense", the immune system can induce the brain to respond to the "danger" of pathogen infection and inflammation, resulting in the orchestration of the febrile response and its subsequent effects on behavior (i.e., sleep and feeding) [4,85]. In contrast, the immune system is regulated by the central nervous system (CNS) in response to environmental stress, either directly via the autonomic nervous system or by way of the hypothalamus-pituitaryadrenal (HPA) axis.…”

“…As such, it is reasonable to think that factors produced by the neuroendocrine system could contribute to the maintenance of immune tolerance. Glucocorticoids and noradrenalin are the classical examples of endogenous immunosuppressive agents produced, by the HPA axis and the sympathetic nervous system respectively, in response to stress or systemic inflammation [4,85]. Furthermore, a number of neuropeptides and hormones have emerged over recent years as potential candidates for the treatment of the unwanted immune responses, which occur in inflammatory and autoimmune disorders, by restoring immune homeostasis [46,85].…”

“…According to this view, while the immune system reacts to exposure to bacteria, viruses and trauma, the neuroendocrine system responds to external stimuli such as temperature, pain and stress. However, it has recently become clear that both systems are involved in a variety of essential, coordinated responses to potential threats.Acting as a "sixth sense", the immune system can induce the brain to respond to the "danger" of pathogen infection and inflammation, resulting in the orchestration of the febrile response and its subsequent effects on behavior (i.e., sleep and feeding) [4,85]. In contrast, the immune system is regulated by the central nervous system (CNS) in response to environmental stress, either directly via the autonomic nervous system or by way of the hypothalamus-pituitaryadrenal (HPA) axis.…”

“…In contrast, the immune system is regulated by the central nervous system (CNS) in response to environmental stress, either directly via the autonomic nervous system or by way of the hypothalamus-pituitaryadrenal (HPA) axis. That these two systems function as a closely linked network is supported by the fact that they both communicate using a mutual biochemical language, involving shared ligands such as neuropeptides, hormones, cytokines and their respective receptors [4]. Thus the traditional distinctions between neuropeptides, hormones and immune mediators are harder to define, raising the question of what can actually be considered as immune or neuroendocrine.…”

CD14 Signaling Reciprocally Controls Collagen Deposition and Turnover to Regulate the Development of Lyme Arthritis

“…In addition to fostering general leukocyte movement, degradation of collagen also liberates small tripeptide fragments such as proline-glycine-proline (PGP), which exhibit an affinity for the chemokine receptors CXCR1/2 as do the neutrophil chemoattractants CXCL8/KC and MIP-2. 15,17,25 The PGP gradient thus formed serves to prolong recruitment of neutrophils even after the CXCL chemokine gradient wanes. 15,17 CD14 is a glycosylphosphatidylinositol-anchored protein expressed primarily on cells of myeloid origin, such as neutrophils, macrophages, and DCs.…”