Miller, Luitpold E. and Grifka, Joachim and Schoelmerich, Juergen and Straub, Rainer H. (2002) Norepinephrine from synovial tyrosine hydroxylase positive cells is a strong indicator of synovial inflammation in rheumatoid arthritis. JOURNAL OF RHEUMATOLOGY, 29 (3). pp. 427-435. ISSN 0315-162X
Full text not available from this repository.Abstract
Objective. Density of sympathetic nerve fibers in synovial tissue was lower in patients with rheumatoid arthritis (RA) compared to those with osteoarthritis (OA). This was accompanied by norepinephrine NE) release from synovial tyrosine hydroxylase positive cells (TH+ cells). We investigated the rule of TH+ cells and NE in synovial inflammation. Methods. Synovial tissue of 34 patients with RA and 36 with OA who underwent knee joint replacement surgery was characterized using immunohistochemistry and a synovial tissue superfusion technique, respectively. In culture experiments with mixed synoviocytes, the effect of NE on secretion of interleukin 6 (IL-6), IL-8, tumor necrosis factor (TNF), and matrix metalloproteinase-3 (MMP-3) was investigated. Results. Tissue density of TH+ cells was higher in RA compared to OA (63.9 vs 34.2 cells/mm(2); p = 0.017). Basal NE release from synovial tissue correlated highly significantly with density of TH+ cells in RA (R-rank = 0.573, p = 0.001) but not in OA (R-rank = 0.102, NS). Basal NE release correlated with the degree of inflammation in RA (R-rank = 0.420, p = 0.021) but not in OA (R-rank = 0.174, NS), and with spontaneous IL-8 secretion in RA (R-rank = 0.581, p = 0.001) but not in OA (R-rank 0.160, NS). Only in RA, density of TH+ cells correlated positively with spontaneous secretion of IL-6, IL-8, and MMP-3. We confirmed the extensive loss of sympathetic nerve fibers in RA compared to OA (0.32 vs 3.1 nerve fiber/mm(2); p < 0.001). The ratio of sympathetic to sensory nerve fibers was I to 5 in RA and 2 to I in OA. A ratio of 1.0 separates almost all patients into 2 diseases groups (RA vs OA). Prior prednisolone treatment of RA patients was related to decreased spontaneous cytokine secretion, a lower density of T cells, CD163+ macrophages and TH+ cells, a lower degree of inflammation, and reduced synovial NE secretion. NE was able to inhibit secretion of IL-6 (in OA), IL-8 (in RA), and TNF (in RA and OA) in culture experiments. Conclusion. TH+ cells and release of NE are strongly linked to a higher degree of synovial inflammation. Culture experiments indicate that NE has anti inflammatory properties at higher concentrations (10(-5) M), NE secretion of TH+ cells may be an antiinflammatory mechanism to counteract local inflammation. Thus, TH+ cell derived NE can be an important local factor of immunomodulation in synovial inflammation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ADENOSINE RECEPTOR AGONISTS; NECROSIS-FACTOR-ALPHA; SUBSTANCE-P; HUMAN-MONOCYTES; MURINE SPLEEN; IN-VITRO; MACROPHAGES; RELEASE; ACTIVATION; TISSUE; rheumatoid arthritis; cytokine; sympathetic nerves; norepinephrine; substance P; matrix metalloproteinase 3 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Nov 2021 16:01 |
| Last Modified: | 08 Nov 2021 16:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/40536 |
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