Neutral endopeptidase (3.4.24.11) in plasma and synovial fluid of patients with rheumatoid arthritis. A marker of disease activity or a regulator of pain and inflammation?
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 (3.4.24.11) (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) of patients with RA when compared to patients with OA (73.4 +/- 22 in plasma and 15.2 +/- 10.8 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Institute of Internal Medicine, University of Cagliari, Italy.
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Matucci-Cerinic
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Lombardi
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Leoncini
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Pignone
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Sacerdoti
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Spillantini
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Partsch
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers; D001799:Blood Sedimentation; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D015260:Neprilysin / Q000097:blood* / Q000378:metabolism* / Q000502:physiology; D010003:Osteoarthritis / Q000097:blood / Q000378:metabolism; D010146:Pain / Q000503:physiopathology; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism; D012016:Reference Values; D012044:Regression Analysis; D013582:Synovial Fluid / Q000378:metabolism*
D015415:Biomarkers; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin