Figure 3.

Acetylcholine (ACh)–induced decrease in the production of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and the chemokines IL-8, monocyte chemotactic protein 1 (MCP-1), RANTES, and macrophage inflammatory protein 1α (MIP-1α) by IL-1–activated fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) and osteoarthritis (OA) patients. A, ACh dose-dependently decreased IL-6 release following IL-1 activation. FLS from 7 RA and 7 OA patients were pretreated with the indicated concentrations of ACh (see Materials and Methods for details) and stimulated with IL-1. No significant difference between OA and RA lines was noted. B, ACh (1 mM) decreased the release of IL-6 even when applied hours after IL-1 stimulation, as measured in 24-hour supernatants from 7 independent FLS lines. C, ACh reduced the release of G-CSF and chemokines in 3 independent FLS lines stimulated for 24 hours with IL-1 in the presence and absence of 1 mM ACh, as determined by multiplex assay. D, The selective α7R agonist PNU-282,987 dose-dependently inhibited IL-6 production in 24-hour supernatants from 7 independent FLS lines. PNU-282,987 (PNU) was added to the culture 1 hour before IL-1 stimulation. Values are the median, with first and third quartiles (lower and upper ends of error bars, respectively). ‡ = P < 0.001; * = P < 0.05 versus controls without ACh, by unpaired t-test.