The synovial expression and serum levels of interleukin‐6, interleukin‐11, leukemia inhibitory factor, and oncostatin m in rheumatoid arthritis

Abstract

Objective. To determine the expression of interleukin‐6 (IL‐6), IL‐11, leukemia inhibitory factor (LIF), and oncostatin M (OSM) and their major cellular sources in the joints of rheumatoid arthritis (RA) patients, as well as the correlation of circulating levels of these IL‐6‐type cytokines and C‐reactive protein (CRP). Methods. Messenger RNA (mRNA) and protein levels for IL‐6, IL‐11, LIF, and OSM were determined by using reverse transcription‐polymerase chain reaction and enzyme‐linked immunosorbent assay, respectively. Results. Cells isolated from the synovium of RA patients expressed mRNA for IL‐6, IL‐11, LIF, and OSM at higher levels than did synovial cells from osteoarthritis (OA) patients, and spontaneously released greater quantities of these proteins in culture. Fibroblast cell lines derived from RA synovium were able to produce IL‐6, IL‐11, and LIF, but not OSM, when stimulated with IL‐1 and tumor necrosis factor α. OSM was found to be produced spontaneously by synovial tissue macrophages. IL‐6, IL‐11, LIF, and OSM were present in synovial fluid from the RA patients; levels of IL‐6, LIF, and OSM were present in significantly greater quantities in RA patients than in OA patients. However, only IL‐6 was significantly elevated in the serum of RA patients and correlated with the serum CRP level, while other IL‐6‐type cytokines were not detected. Conclusion. IL‐6, IL‐11, LIF, and OSM are all produced in large amounts at the site of disease activity, but IL‐6 derived from synovial fibroblasts may be the major hormone‐like mediator that induces the hepatic synthesis of acute‐phase proteins in RA.

Induction of CCL13 expression in synovial fibroblasts highlights a significant role of oncostatin M in rheumatoid arthritis

“…It is secreted by activated T cells, monocytes, and neutrophils (13,14,41), and elevated levels of OSM are detected in the synovial fluid of patients with RA but not OA (9,10). Earlier studies clearly showed that OSM production in RA tissue correlated with the amount of leukocyte infiltration (9).…”

“…Nevertheless, these therapeutic strategies are not beneficial to all patients, suggesting that other players must be involved in the pathogenesis. Various studies have shown that other cytokines such as IL-6, oncostatin M (OSM), IL-4, IL-13, and interferon-␥ (IFN␥) are also present in the synovial fluid of chronically inflamed joints (9)(10)(11).…”

Cyclosporine differentially regulates interleukin-10, interleukin-15, and tumor necrosis factor ? production by rheumatoid synoviocytes

“…They strongly express a variety of activation markers, including surface molecules (e.g., major histocompatibility complex class II, CD13, or vascular cell adhesion molecule 1), and can thereby efficiently present antigens to T cells. In addition, fibroblast cell lines isolated from RA patients have the potential to produce matrix-degrading enzymes and several cytokines, such as IL-1, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and transforming growth factor ␤ (TGF␤) (31)(32)(33). In this study, we demonstrated that FLS were able to secrete large amounts of IL-15 and TNF␣, which were strongly induced by treatment with IL-1␤, IFN␥, and LPS.…”

Leukemia Inhibitory Factor, Interleukin 6, and Other Cytokines Using the GP130 Transducing Receptor: Roles in Inflammation and Injury

“…Many studies report that LIF is a pro-inflammatory mediator in a variety of inflammatory disorders (Table 1), while others point to an anti-inflammatory role ( Table 2). LIF is highly elevated in the synovial tissue and fluids of patients with rheumatoid arthritis [68][69][70]. In addition, human articular chondrocytes and synoviocytes produce LIF, which is strongly upregulated by other proinflammatory cytokines, such as IL-1, IL-6, IL-17, or TNF [71,72] and downregulated by the antiinflammatory cytokine IL-4 [73].…”