PMID- 11908553
OWN - NLM
STAT- MEDLINE
DCOM- 20020924
LR  - 20181130
IS  - 0315-162X (Print)
IS  - 0315-162X (Linking)
VI  - 29
IP  - 3
DP  - 2002 Mar
TI  - Norepinephrine from synovial tyrosine hydroxylase positive cells is a strong 
      indicator of synovial inflammation in rheumatoid arthritis.
PG  - 427-35
AB  - 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 role 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/mm2; p = 0.017). Basal 
      NE release from synovial tissue correlated highly significantly with density of 
      TH+ cells in RA (Rrank = 0.573, p = 0.001) but not in OA (Rrank = 0.102, NS). 
      Basal NE release correlated with the degree of inflammation in RA (Rrank = 0.420, 
      p = 0.021) but not in OA (Rrank = 0.174, NS), and with spontaneous IL-8 secretion 
      in RA (Rrank = 0.581, p = 0.001) but not in OA (Rrank = 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/mm2; p < 0.001). The ratio of 
      sympathetic to sensory nerve fibers was 1 to 5 in RA and 2 to 1 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 antiinflammatory 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.
FAU - Miller, Luitpold E
AU  - Miller LE
AD  - Department of Internal Medicine I, University Medical Center Regensburg, Germany.
FAU - Grifka, Joachim
AU  - Grifka J
FAU - Scholmerich, Jurgen
AU  - Scholmerich J
FAU - Straub, Rainer H
AU  - Straub RH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Canada
TA  - J Rheumatol
JT  - The Journal of rheumatology
JID - 7501984
RN  - 0 (Biomarkers)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 33507-63-0 (Substance P)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
EIN - J Rheumatol. 2003 May;30(5):1125
MH  - Adrenergic Fibers/chemistry/enzymology/pathology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Arthritis, Rheumatoid/*immunology/metabolism/*pathology
MH  - Biomarkers
MH  - Cell Count
MH  - Cells, Cultured
MH  - Humans
MH  - Interleukin-6/analysis/metabolism
MH  - Interleukin-8/analysis/metabolism
MH  - Matrix Metalloproteinase 3/analysis/metabolism
MH  - Middle Aged
MH  - Norepinephrine/*analysis/metabolism
MH  - Osteoarthritis/immunology/pathology
MH  - Predictive Value of Tests
MH  - Substance P/analysis
MH  - Synovial Membrane/immunology/innervation/*pathology
MH  - Tumor Necrosis Factor-alpha/analysis/metabolism
MH  - Tyrosine 3-Monooxygenase/*analysis
EDAT- 2002/03/23 10:00
MHDA- 2002/09/25 06:00
CRDT- 2002/03/23 10:00
PHST- 2002/03/23 10:00 [pubmed]
PHST- 2002/09/25 06:00 [medline]
PHST- 2002/03/23 10:00 [entrez]
PST - ppublish
SO  - J Rheumatol. 2002 Mar;29(3):427-35.