In Vitro Superfusion Method to Study Nerve‐Immune Cell Interactions in Human Synovial Membrane in Long‐standing Rheumatoid Arthritis or Osteoarthritisa

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Abstract
Reports on patients with hemiparalysis indicate the importance of the nervous system for the pathophysiology of rheumatoid arthritis (RA) or osteoarthritis (OA). Norepinephrine (NE) and opioids seem to be more anti‐inflammatory neurotransmitters whereas substance P is proinflammatory. The study aimed to investigate the direct noradrenergic nerve‐immune cell interaction in human synovial membrane. We used a recently developed superfusion technique with electrical stimulation of synovial membrane to elicit local NE from synovial membrane slices. The readout parameter of synovial immune cells was interleukin‐6 (IL‐6). IL‐6 was spontaneously secreted from RA and OA synovial membranes. Electrical field stimulation intensively reduced IL‐6 secretion. In patients with OA or RA, this electrically induced reduction of IL‐6 secretion was not significantly changed by α‐ or β‐adrenergic antagonists. The study demonstrates that local endogenous NE seem to play a minor role, which may be due to a depletion of NE or loss of noradrenergic fibers during chronic RA and OA.