Rheumatology International

, Volume 13, Issue 1, pp 1-4

First online:

Neutral endopeptidase ( in plasma and synovial fluid of patients with rheumatoid arthritis. A marker of disease activity or a regulator of pain and inflammation?

  • M. Matucci-CerinicAffiliated withInstitute of Internal Medicine, University of Cagliari
  • , A. LombardiAffiliated withInstitute of Internal Medicine IV, University of Florence
  • , G. LeonciniAffiliated withInstitute of Internal Medicine IV, University of Florence
  • , A. PignoneAffiliated withInstitute of Internal Medicine IV, University of Florence
  • , L. SacerdotiAffiliated withInstitute of Internal Medicine IV, University of Florence
  • , M. G. SpillantiniAffiliated withMedical Research Council, Molecular Neurobiology Unit, University of Cambridge
  • , G. PartschAffiliated withLudwig Boltzmann Institute for Rheumatology

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access


In recent years the role of the peripheral nervous system has been focused on the pathogenesis of rheumatoid arthritis (RA). In particular, substance P (SP), released by the sensory terminals, has been demonstrated to be involved in cartilage breakdown [13]. The aim of our work was to study the levels of SP and its peptidases, neutral endopeptidase ( (NEP) and angiotensin-converting enzyme (ACE), in the synovial fluid and plasma of 30 patients with RA and 14 patients with osteoarthritis (OA). ACE and NEP were determined with a fluorimetric assay and SP with a radioimmunoassay (RIA) method. ACE levels were normal in the plasma of patients with RA and OA (6.1±1.9 and 6.7±1.4 pmol/ml/min, respectively); we found no differences in the values, of ACE between RA and OA synovial fluid (5.7±4.2 and 5.5±4.1 pmol/ml/min, respectively). NEP levels were significantly increased in plasma (139.3±36 pmol/ml/min) and synovial fluid (133.8±32 pmol/ml/min in synovial fluid) and healthy controls (89.7±14 pmol/ml/min in plasma). In synovial fluid, SP was significantly higher in RA patients (43.1±16.6 pg/ ml) than in OA patients (12±13.1 pg/ml), while plasma levels did not show any difference (RA: 14.4±10.2; OA: 13.6±10.6; healthy subjects: 11.3±3.9 pg/ml). The only relationship detected in controls and in OA was among plasma NEP and ESR (P<0.05) and synovial fluid NEP (P<0.001). Our data confirmed that SP could have a role in the pathogenesis of RA synovial inflammation through a control on neurogenic inflammation (SP degradation), vascular tone control (endothelin degradation) and on nociception (enkephalin degradation).

Key words

Neutral endopeptidases Substance P Rheumatoid arthritis Angiotensin converting enzyme Neurogenic inflammation Nociception