No disease-specific pattern in the phenotype of apoptotic synovial lining cells could be suggested in any of the inflammatory arthritides studied. However, topological differences in the lining and quantitative differences in the inflammatory cell apoptosis in synovial stroma may in part explain the occurrence of the prominent synovial lining cell hyperplasia distinguishing RA from ReA and PsA. On the other hand, relatively frequent inflammatory cell apoptosis may contribute both to the downregulation of synovial inflammation and to the control of synovial lining hyperplasia in ReA.
Substance P (SP) and somatostatin (SOM) have been identified in a distinct subpopulation of dorsal root sensory neurons and their peripheral endings.' Nerve fibers, stained for SP, have been observed in human joint synovia.' The role of peptidergic sensory neurons and of the "neurogenic inflammation" in rheumatoid arthritis (RA) and, particularly, in the involvement of SP in the articular destruction in experimental arthritis has been dem~nstrated.~" High levels of SP have been detected in synovial fluid (SF) of rheumatoid arthritis patients.6 We have assayed the SF levels of SP and SOM in patients affected with inflammatory joint diseases [RA and psoriatic arthritis (PA)] and degenerative joint disease [osteoarthritis (OA)].
PATIENTS AND METHODSThe SF samples were obtained by knee arthrocentesis from 18 patients with RA, 12 patients with OA, and 8 patients with PA. SF samples were collected in ice and were immediately frozen. SP and SOM immunoreactivities (SP-LI, SOM-LI) were assayed, in ethanol acid extracts, by radioimmunoassay (Amersham, United Kingdom; sensitivity of the assay was 1.1 fmol/tube for SP-LI and 0.8 fmol/tube for SOM-LI). Differences among groups were evaluated using Student's t test. Logarithmic regression analyses were used to compare the value of the erythrocyte sedimentation rate (ESR) and the SF neuropeptide levels.
RESULTSThe SP-LI (pmol/mL) mean level was significantly higher in RA (P) (43.1 ? 9.8) than in OA (12.0 * 1.3) or PA (24.7 * 1.8). Likewise, SOM-LI was higher in RA (P) (22.8 +-1.4) than in OA (13.6 2 4.7) or PA (14.7 2 4.8). A significant correlation was found between the ESR and SP levels in RA SF (r = 0.447P).
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ANNALS NEW YORK ACADEMY OF SCIENCES
DISCUSSIONThe present data about higher SP levels in the SF of RA patients are in agreement with previous reports.' Various evidences indicate that SP is involved in the joint inflammatory process in rheumatic disease^.^" It may be hypothesized that the higher SP-LI levels detected in RA SF could be related with the intense inflammation of the knee joint of RA patients. We have demonstrated that intraarticular SOM induces a clinical improvement in RA patients.' The observation that SOM inhibits SP release from sensory nerves' might have some relationship with the high SOM-LI levels that we have detected in the SF of RA patients. Furthermore, the correlation between the high level of SP and the increase in ESR, a specific index of inflammation, further suggests that this peptide represents an important agent in the development of rheumatic disease.
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