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Drugs that Target Sympathetic–Immune Pathways for Treatment of Autoimmune Diseases

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Handbook of Neurochemistry and Molecular Neurobiology

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Abstract:

Autoimmune disorders often share two common characteristics, dysregulation of the immune system and the nervous system stress pathways, the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. Dysregulation of these systems are likely to be functionally related, as there is bidirectional communication between the immune system and the central nervous system (CNS). The CNS modulates immune function by signaling target cells of the immune system through autonomic and neuroendocrine pathways. These immune cells relay information back to autonomic, limbic, and cortical areas of the CNS to affect neural activity and consequently modify behavior, hormone release, and autonomic function (Besedovsky and del Rey, 1996; Maier and Watkins, 1998). In this manner, immune cells function as a sense organ, informing the CNS of peripheral events relating to infection and injury. Equally important, homeostatic mechanisms are needed at all levels to turn off the immune response when the pathogen and injurious condition are eliminated and the repair process is completed. In individuals with rheumatoid arthritis (RA) and other autoimmune diseases, there is a failure of the homeostatic regulation leading to long-term immune activation that has serious health consequences.

This chapter summarizes changes that occur in SNS to immune signaling in autoimmune diseases using RA as a specific example and presenting similarities of other autoimmune disease. Evidence that the SNS can enhance or suppress inflammation and immune function, that SNS dysregulation is a critical component of the immune system dysregulation which drives RA pathology, and that the SNS may be targeted in RA to restore immune system homeostasis and prevent disease pathology, will be presented. The potential for using drugs that target the SNS to treat RA and other autoimmune diseases also will be explored.

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Abbreviations

AA:

adjuvant‐induced arthritis

ACTH:

adrenocorticotrophic hormone

ANS:

autonomic nervous system

AR:

adrenergic receptor

CFA:

complete Freund's adjuvant

CIA:

collagen‐induced arthritis

CNS:

central nervous system

Con A:

concanavalin

CREAE:

experimental allergic encephalomyelitis

CRH:

corticotrophin releasing hormone

DTH:

delayed‐type hypersensitivity

EAE:

experimental allergic encephalomyelitis

EAMG:

experimental autoimmune myasthenia gravis

EPI:

epinephrine

HPA:

hypothalamic‐pituitary‐adrenal

IFN:

Interferon

Ig:

immunoglobulin

IL:

Interleukin

KLH:

keyhole limpet hemocyanin

LPS:

lipopolysaccharide

MHPG:

metabolite, 3‐methoxy‐4‐hydroxy‐phenylglycol

NA:

noradrenergic

NE:

norepinephrine

NGF:

nerve growth factor

NK:

natural killer

NPY:

neuropeptide Y

PBMC:

peripheral blood mononuclear leukocytes

PFC:

plaque‐forming cell

PNS:

parasympathetic nervous system

PVN:

paraventricular nucleus

RA:

rheumatoid arthritis

RBC:

red blood cells

SEB:

staphylococcal enterotoxin

6‐OHDA:

6‐hydroxydopamine

SNS:

sympathetic Nervous System

SWC:

streptococcal cell wall‐induced arthritis

SympX:

sympathectomy

TH:

tyrosine hydroxylase

TNF:

tumor necrosis factor

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Acknowledgments

We acknowledge Boswell Memorial Hospital imaging for kindly providing the facilities and expert technical assistance with the X-rays critical for evaluation of arthritis development for our studies. This research was supported by Sun Health Research Institute, R29 MH 49050; Arizona Disease Control Research Commission grant 9614; and a grant from the Sun City West Community Fund. We wish to thank Mary Michaels for her assistance with the database for preparation of the reference list.

Authors
  1. D. Lorton
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  2. C. Lubahn
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  3. D. Bellinger
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, New York, Orangeburg, USA

    Abel Lajtha (Director) (Director)

  2. The Buniatian Institute of Biochemistry the National Academy of Sciences, 5/1 Sevag str., 375014, Yerevan, Republic of Armenia

    Armen Galoyan

  3. Dept. Immunophysiology Medical Faculty, Inst. of Normal and Pathological Physiology, Deutschhausstrase 2, D–35037, Marburg, Germany

    Hugo O. Besedovsky

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Lorton, D., Lubahn, C., Bellinger, D. (2008). Drugs that Target Sympathetic–Immune Pathways for Treatment of Autoimmune Diseases. In: Lajtha, A., Galoyan, A., Besedovsky, H.O. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30398-7_5

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