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Neuroendocrine–immune interactions in synovitis

Nature Clinical Practice Rheumatology volume 3, pages 627–634 (2007)Cite this article

Abstract

Synovial tissue lines the noncartilaginous surfaces of synovial joints and supplies these avascular structures with nutrients. In diseases such as rheumatoid arthritis, inflammation of the synovial tissue—synovitis—induces diffuse damage to the joints. The presence of functional receptors for glucocorticoids, androgens and estrogens in synoviocytes might link inflammation and the endocrine system at the local level. Synovial tissue could be regarded as an intracrine tissue, whereby active steroids influence the cells in which they are synthesized, without their release into the extracellular space. An increase in the peripheral metabolism of sex steroids is characteristic of rheumatoid synovitis, with an augmented ratio of estrogen to androgen occurring in both male and female patients. Changes in the peripheral nervous system at the site of local inflammation are also hallmarks of synovitis in rheumatoid arthritis. In the chronic phase of synovitis, sympathetic nerve fibers are lost; by contrast, sensory nerve fibers sprout into the inflamed tissue. Complex interactions occur between the endocrine, nervous and immune systems during synovitis. In particular, studying neuroendocrine–immune interactions in the inflamed synovium will potentially uncover new mechanisms in the pathophysiology of rheumatoid arthritis and might lead to new methods of therapeutic intervention.

Key Points

  • The presence of functional glucocorticoid, androgen and estrogen receptors in synoviocytes links the endocrine system and the immune response/inflammation at a local level

  • The synovial tissue might be considered as an intracrine tissue, whereby the effects of active steroids occur in the same cells in which they are made

  • Increased peripheral metabolism of sex steroids occurs in rheumatoid synovitis, with an augmented estrogen to androgen ratio in both sexes

  • Changes in the peripheral nervous system at the site of local inflammation are also hallmarks of synovitis in rheumatoid arthritis

  • Complex and changing interactions between the endocrine, nervous and immune systems occur during synovitis

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Figure 1: Neuroendocrine pathways in synovitis.
Figure 2: Steroid hormone secretion and metabolism.
Figure 3: Immune–endocrine interactions in synovitis.

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Author information

Authors and Affiliations

  1. M Cutolo is Full Professor of Rheumatology and Director of the Research Laboratory in the Academic Clinical Division and Postgraduate School of Rheumatology at the University of Genova, Italy.,

    Maurizio Cutolo

  2. RH Straub is Professor of Experimental Medicine and Head of the Research Laboratories in the Department of Internal Medicine I at University Hospital Regensburg, Germany.,

    Rainer H Straub

  3. JWJ Bijlsma is Full Professor and Head of the Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, The Netherlands.,

    Johannes WJ Bijlsma

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  1. Maurizio Cutolo
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Correspondence to Maurizio Cutolo.

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Cutolo, M., Straub, R. & Bijlsma, J. Neuroendocrine–immune interactions in synovitis. Nat Rev Rheumatol 3, 627–634 (2007). https://doi.org/10.1038/ncprheum0601

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