Rheumatology International

, Volume 13, Issue 1, pp 1–4 | Cite as

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-Cerinic
  • A. Lombardi
  • G. Leoncini
  • A. Pignone
  • L. Sacerdoti
  • M. G. Spillantini
  • G. Partsch


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 


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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • M. Matucci-Cerinic
    • 1
  • A. Lombardi
    • 2
  • G. Leoncini
    • 2
  • A. Pignone
    • 2
  • L. Sacerdoti
    • 2
  • M. G. Spillantini
    • 3
  • G. Partsch
    • 4
  1. 1.Institute of Internal MedicineUniversity of CagliariItaly
  2. 2.Institute of Internal Medicine IVUniversity of FlorenceItaly
  3. 3.Medical Research Council, Molecular Neurobiology UnitUniversity of CambridgeUnited Kingdom
  4. 4.Ludwig Boltzmann Institute for RheumatologyWien-OberlaaAustria

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