Catecholamine-producing cells in the synovial tissue during arthritis: modulation of sympathetic neurotransmitters as new therapeutic target

Capellino, Silvia; Cosentino, Marco; Wolff, Christine; Schmidt, Martin; Grifka, Joachim; Straub, Rainer H.

doi:10.1136/ard.2009.119701

Cited by 112 publications

(125 citation statements)

References 23 publications

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“…Applying a model of repetitive electric PNS resembling sustained splanchnic vascular SNS activity, we report that cirrhotic rats display almost doubled and about 30% increased NA release caused by first and subsequent PNS, respectively. This apparent discrepancy can potentially be explained by peripheral immune cells being equipped with catecholamine synthesizing enzymes [23]. Indirect evidence also shows neurotransmitter release from immune cells in response to electrical stimulation [24].…”

Section: Discussionmentioning

confidence: 99%

Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: Impact of exogenous neuropeptide Y

Dietrich¹,

Moleda²,

Kees

et al. 2013

Journal of Hepatology

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Section: Discussionmentioning

confidence: 99%

Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: Impact of exogenous neuropeptide Y

Dietrich¹,

Moleda²,

Kees

et al. 2013

Journal of Hepatology

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“…In addition, the effect of cytoplasmic catecholamine increase was tested in vivo in CIA in mice. It was found that local treatment with reserpine markedly reduced inflammation without causing systemic side effects in the animals (41). This indicates that when sympathetic nerve fibers are lost in inflamed tissue, sympathetic cells can take over.…”

Section: Sympathetic Innervation Of the Spleen And Joints In Experimementioning

confidence: 93%

“…Similarly, the number of sympathetic nerve fibers in the joints of RA patients is reduced significantly, coinciding with an increased degree of inflammation, but also with significantly more substance P-positive nerve fibers and an augmented NE production by synovial cells (macrophages, B cells, fibroblasts, mast cells and granulocytes) (9,40,41). Moreover, in AIA rats, ankle joints that developed more severe arthritis were more densely innervated by substance P-containing, primary afferent neurons than were joints that developed less severe arthritis (knees) (42).…”

Section: Sympathetic Innervation Of the Spleen And Joints In Experimementioning

confidence: 99%

“…Moreover, in patients with RA, who markedly lose sympathetic nerve fibers, the density of catecholamineproducing cells was higher than in patients with OA, who do not lose sympathetic innervation. Blockade of catecholamine storage into vesicles by reserpine caused a very strong and specific inhibition of TNF-α mRNA and TNF-α protein from cells of patients with OA and RA (41). In addition, the effect of cytoplasmic catecholamine increase was tested in vivo in CIA in mice.…”

Section: Sympathetic Innervation Of the Spleen And Joints In Experimementioning

confidence: 99%

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Restoring the Balance of the Autonomic Nervous System as an Innovative Approach to the Treatment of Rheumatoid Arthritis

Koopman

Stoof

Straub

et al. 2011

Mol Med

128

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The immunomodulatory effect of the autonomic nervous system has raised considerable interest over the last decades. Studying the influence on the immune system and the role in inflammation of the sympathetic as well as the parasympathetic nervous system not only will increase our understanding of the mechanism of disease, but also could lead to the identification of potential new therapeutic targets for chronic immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). An imbalanced autonomic nervous system, with a reduced parasympathetic and increased sympathetic tone, has been a consistent finding in RA patients. Studies in animal models of arthritis have shown that influencing the sympathetic (via α-and β-adrenergic receptors) and the parasympathetic (via the nicotinic acetylcholine receptor α7nAChR or by electrically stimulating the vagus nerve) nervous system can have a beneficial effect on inflammation markers and arthritis. The immunosuppressive effect of the parasympathetic nervous system appears less ambiguous than the immunomodulatory effect of the sympathetic nervous system, where activation can lead to increased or decreased inflammation depending on timing, doses and kind of adrenergic agent used. In this review we will discuss the current knowledge of the role of both the sympathetic (SNS) and parasympathetic nervous system (PNS) in inflammation with a special focus on the role in RA. In addition, potential antirheumatic strategies that could be developed by targeting these autonomic pathways are discussed.

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“…In rheumatology, adrenergic stimulation has been associated with proinflammatory effects in acute diseases and anti-inflammatory effects in chronic diseases (18). Sympathetic activation, as induced by psychological stress, has been linked to chronic low-grade inflammatory diseases, such as DMT2, cardiovascular diseases, RA and the modulation of multiple sclerosis (19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Adrenergic stimulation alters the expression of inflammasome components and interleukins in primary human monocytes

Horstmann

Marzi

Relja

2015

Experimental and Therapeutic Medicine

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Abstract. Prior to their release, interleukin (IL)-1β and IL-18 are cleaved to their bioactive forms by a multiprotein complex known as an inflammasome, which is comprised of a number of elements that are subject to nuclear factor-κB-dependent transcription. Catecholamines have been indicated to exert an enhancing effect on the IL-1β release. The aim of the present study was to determine whether alterations in inflammasome gene expression may be responsible for the modified IL-1β and IL-18 secretion following lipopolysaccharide (LPS) and catecholamine co-stimulation. Monocytes were isolated from the peripheral blood of 21 healthy volunteers using CD14 + microbeads. Following stimulation with LPS (2 µg/ml) and/or phenylephrine (PE; 10 µM) for 24 h, the supernatants were subjected to ELISA to evaluate the ex vivo protein expression levels of IL-1β and IL-18. In addition, the gene expression levels of inflammasome components associated with the cleavage of IL-1β and IL-18, including NLRP1, NLRP3, caspase-1 and PYCARD were determined using polymerase chain reaction. The results indicated that LPS significantly increased IL-1β expression compared with the unstimulated control samples. Co-stimulation with LPS + PE significantly enhanced IL-1β expression compared with LPS alone. Furthermore, IL-18 expression was significantly reduced by LPS and LPS + PE co-stimulation. The gene expression levels of IL-18, NLRP1, caspase-1 and PYCARD were comparable in the LPS-and LPS + PE-stimulated cells. LPS significantly induced the expression levels of IL-1β and NLRP3, and to a lesser degree, the expression of NLRP1, compared with the control. By contrast, PE markedly induced the expression levels of IL-18 and NLRP1, while LPS reduced the gene expression of IL-18. In conclusion, adrenergic stimulation suppressed NLRP3 expression and enhanced NLRP1 expression, indicating that NLRP3 may regulate IL-1β secretion and NLRP1 may regulate the release of IL-18.

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Catecholamine-producing cells in the synovial tissue during arthritis: modulation of sympathetic neurotransmitters as new therapeutic target

Abstract: This study demonstrates that local catecholamine-producing cells start to replace sympathetic nerve fibres around the onset of disease, and modulation of locally produced catecholamines has strong anti-inflammatory effects in vivo and in vitro.

Cited by 112 publications

References 23 publications

Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: Impact of exogenous neuropeptide Y

Dysbalance in sympathetic neurotransmitter release and action in cirrhotic rats: Impact of exogenous neuropeptide Y

Restoring the Balance of the Autonomic Nervous System as an Innovative Approach to the Treatment of Rheumatoid Arthritis

Adrenergic stimulation alters the expression of inflammasome components and interleukins in primary human monocytes

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