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 foc used on the pathogenesis of rheumatoid arthritis (RA). In particular, substance P (SP), released by the sensory terminals, has been demonstr ated to be involved in cartilage breakdown [13]. The aim of our work w as to study the levels of SP and its peptidases, neutral endopeptidase (3.4.24.11) (NEP) and angiotensin-converting enzyme (ACE), in the syn ovial fluid and plasma of 30 patients with RA and 14 patients with ost eoarthritis (OA). ACE and NEP were determined with a fluorimetric assa y 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 p atients 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 significan tly 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 o nly relationship detected in controls and in OA was among plasma NEP a nd ESR (P < 0.05) and synovial fluid NEP (P < 0.001). Our data confirm ed that SP could have a role in the pathogenesis of RA synovial inflam mation through a control on neurogenic inflammation (SP degradation), vascular tone control (endothelin degradation) and on nociception (enk ephalin degradation).