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.

Objective. To investigate the role of interleukin-6 (IL-6) and transforming growth factor pl (TGFp1) in the regulation of tissue inhibitor of metalloproteinases-1 (TIMP-1) synthesis in human articular chondrocytes.Methods. Articular cartilage was obtained from human knee joints 24 hours after death. Chondrocytes were isolated by collagenase digestion and embedded in low-gellingtemperature agarose. After stimulation by cytokines, total RNA was isolated and analyzed by Northern blotting. TIMP-1 protein levels were determined using a competitive enzyme-linked immunosorbent assay.Results. Human chondrocytes in agarose culture expressed messenger RNA (mRNA) for the IL-6 receptor (gp80) and its signal-transducing subunit gp130. In contrast to the findings in a previous study, IL-6 did not stimulate TIMP-1 expression in these cells, whereas TGFPl was an important inducer of TIMP-1 mRNA and protein synthesis.Conclusion. Our findings suggest that TGFBl

We have constructed on the cDNA level deletion mutants of human interleukin-6 lacking one, two, three or four amino acids from the carboxyterminus of the molecule. After in vitro transcription and translation the biological activity of these deletion mutants was determined by two independent bioassays. Both, the mouse B9 cell proliferation assay and the fibrinogen induction assay with the human hepatoma cell line HepG2 led to the following result: already the removal of the last amino acid resulted in a five-fold loss of biological activity. An additional slight reduction was seen when two amino acids were removed from the carboxy-terminus. Interleukin-6 lacking three or four C-terminal amino acids were completely inactive. The presented results emphasize the extreme importance of the carboxy-terminus of interleukin-6 for its biological function.

Increased concentrations of interleukin‐6 (IL‐6) have been found in the synovial fluid of patients with osteoarthritis, rheumatoid arthritis and crystal‐related joint deseases. It is therefore of great interest to identify the cells responsible for the production of IL‐6, and to investigate whether IL‐6 plays a role in the pathogenesisof degenerative or inflammatory joint diseases. Here we show that human interleukin‐1β (IL‐1β) induces IL‐6 synthesis and secretion in differentiated human chondrocytes. In organ cultures resembling closely the in vivo system 106 chondrocytes incubated with 100 units of interleukin‐1β per ml of medium led to the release of 6 × 103 units of IL‐6 within 24 h. Chondrocytes cultured in agarose or as monolayers similary incubated with IL‐1β produced even higher amounts of IL‐6: 70 × 103 units per 106 cells within 24 h. The induction of IL‐6 synthesis by IL‐1β was also shown at the mRNA level. IL‐6 secreted by stimulated chondrocytes showed heterogeneity upon Western blot analysis.