Interleukin-6 in synovial fluid is closely associated with chronic synovitis in rheumatoid arthritis

Abstract

Interleukin-6 (IL-6) was detected at low levels in plasma [0.014 +/- 0.006 ng/ml (mean +/- SEM] and in high amounts in synovial fluid [SF; 2.6 +/- 2.2 ng/ml (mean +/- SEM)] of patients with rheumatoid arthritis. No correlation of IL-6 levels in plasma or SF with the ESR (n = 15) or with histological parameters of acute local synovitis (n = 10) was observed. In contrast, SF IL-6 was positively correlated with histological characteristics of chronic synovitis (n = 10; P < or = 0.01) and elevated plasma IgG concentrations (n = 15; P < or = 0.05). In vitro concentrations of IL-6 comparable to those detected in SF increased the production of both IgG and IgM by synovial membrane mononuclear cells. The present results contribute to the view that high local IL-6 concentrations in SF promote chronic synovitis in RA.

Targeting Interleukin-6 in Rheumatoid Arthritis

“…Excess production of IL-6 has been found in the synovial fluid and blood of RA patients and correlates with the disease activity and joint destruction [15,16]. IL-6 promotes synovitis by inducing neovascularisation via vascular endothelial growth factor (VEGF)-stimulated pannus proliferation, resulting in infiltration of inflammatory cells and synovial hyperplasia [17].…”

Interleukin‐8, Interleukin‐10, Intercellular Adhesion Molecule‐1 and Vascular Cell Adhesion Molecule‐1 Expression Levels are Higher in Synovial Tissue from Patients with Rheumatoid Arthritis than in Osteoarthritis

“…Thus, T-cell and neutrophil chemotaxis, a crucial process for leucocyte accumulation, is predominantly induced by interleukin (IL)-8 [6][7][8][9][10]. Other cytokines, such as IL-1, IL-6, tumour necrosis factor-␣ (TNF-␣), granulocyte and monocyte colony-stimulating factor (GM-CSF), transforming growth factor-␤ (TGF-␤) and IL-10, have also been detected in the RA joint [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Overexpression of IL-1␣, IL-1␤, IL-6, TNF-␣, GM-CSF and epidermal growth factor (EGF) has been described in OA synovium [4,[24][25][26].…”

Modulation of hu/mu severe combined immunodeficient (SCID) mouse arthritis by local application of human recombinant IL-1β, IL-2 and IL-6

“…This concentration is a hundred times higher than we used. On the other hand, the applied concentration of IL-6 in our experiments was higher than in synovial fluid of patients with RA [50], and so biological activity was to be expected. We would argue that the concentration of IL-6 is not the limiting factor.…”

“…This could be due to missing costimulatory signals. Sack et al showed that IL-6 stimulates immunoglobulin production of isolated lymphocytes from RA-SM only when the cells are additionally incubated with phorbol myristate acetate (PMA) [50].…”