PDFlib PLOP: PDF Linearization, Optimization, Protection Page inserted by evaluation version www.pdflib.com – [email protected]
Substance P and Somatostatin Levels in Rheumatoid Arthritis, Osteoarthritis, and Psoriatic Arthritis Synovial Fluid S. MARMINI? M. MATUCCI-CERINIC? P. GEPPETlT? E. DEL BIANCO: A. MARCHESONI,~s. TOSI,~ M. CAGNONI," AND G. PARTSCH' ahstitUte of Internal Medicine and Therapeutics IV University of Florence 50139 Florence, Italy hlnstitute of Rheumatology University of Milan Milan, Italy CLudwigBoltzmann Institute of Rheumatology Wien. Austria 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 METHODS
The 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.
RESULTS
The 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).
*
*
435
436
ANNALS NEW YORK ACADEMY OF SCIENCES
DISCUSSION The present data about higher SP levels in the SF of RA patients a r e 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. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8.
HOKFELT, T., R. ELDEef al. 1976. J. Neurosci. 1: 131-136. et al. 1988. J. Rheumatol. 15: 1807-1810. GRONBLAD, M., Y. T. KONITINEN LEVINE, J. D., D. R. CLARK ef al. 1984. Science 226 547-549. LEVINE, J. D., D. H. COLLIER ef al. 1985. J. Rheumatol. 12: 406-411. LEVINE, J. D., S. J. DARDICK ef a/. 1986. J. Neurosci. 6: 3423-3429. P., B. WEILL ef al. 1987. N. Engl. J. Med. 314 1323. DEVILLIER, M. & S. MARABINI. 1988. Med. Sci. Res. 1 6 233-234. MATUCCI-CERINIC, LEMBECK, F., J. DONNERERef a/. 1982. Eur. J. Pharmacol. 85: 171-176.
Substance P and Somatostatin Levels in Rheumatoid Arthritis, Osteoarthritis, and Psoriatic Arthritis Synovial Fluid S. MARMINI? M. MATUCCI-CERINIC? P. GEPPETlT? E. DEL BIANCO: A. MARCHESONI,~s. TOSI,~ M. CAGNONI," AND G. PARTSCH' ahstitUte of Internal Medicine and Therapeutics IV University of Florence 50139 Florence, Italy hlnstitute of Rheumatology University of Milan Milan, Italy CLudwigBoltzmann Institute of Rheumatology Wien. Austria 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 METHODS
The 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.
RESULTS
The 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).
*
*
435
436
ANNALS NEW YORK ACADEMY OF SCIENCES
DISCUSSION The present data about higher SP levels in the SF of RA patients a r e 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. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8.
HOKFELT, T., R. ELDEef al. 1976. J. Neurosci. 1: 131-136. et al. 1988. J. Rheumatol. 15: 1807-1810. GRONBLAD, M., Y. T. KONITINEN LEVINE, J. D., D. R. CLARK ef al. 1984. Science 226 547-549. LEVINE, J. D., D. H. COLLIER ef al. 1985. J. Rheumatol. 12: 406-411. LEVINE, J. D., S. J. DARDICK ef a/. 1986. J. Neurosci. 6: 3423-3429. P., B. WEILL ef al. 1987. N. Engl. J. Med. 314 1323. DEVILLIER, M. & S. MARABINI. 1988. Med. Sci. Res. 1 6 233-234. MATUCCI-CERINIC, LEMBECK, F., J. DONNERERef a/. 1982. Eur. J. Pharmacol. 85: 171-176.
