Concentrations and Origins of Soluble Interleukin 6 Receptor-alpha in Serum and Synovial Fluid

Objective: To determine levels of soluble interleukin 6 receptor-alpha (sIL-6R alpha) in synovial fluid (SF) and serum from patients with different rheumatic diseases, and to analyze its cellular origin compared to IL-6.

Methods: IL-6 and sIL-6R alpha concentrations were measured in sera, SF, and culture supernatants of different cells types using specific sandwich ELISA.

Results: IL-6 levels were significantly higher (30 to 1000-fold) in SF than in sera, and higher in inflammatory arthropathies such as rheumatoid arthritis (RA), chondrocalcinosis, and gout than in osteoarthritis (OA). sIL-6R alpha levels in SF from patients with RA, gout, and chondrocalcinosis were also higher (24.7 +/- 7.5, 23.2 +/- 9.1, and 19.5 +/- 7.4 ng/ml, respectively) than in patients with OA (10.1 +/- 5 ng/ml), although the difference was distinctly smaller. In contrast, sIL-6R alpha concentrations did not differ significantly between the sera of healthy donors and patients. sIL-6R alpha levels were similar in SF and sera from inflammatory arthropathies, but lower in all osteoarthritic SF, compared to their corresponding serum. In contrast to IL-6, sIL-6R alpha was produced in high amounts by hepatocytes but not by structural cells of the joint (chondrocytes, synoviocytes, fibroblasts, and endothelial cells). Polymorphonuclear cells and mononuclear cells released intermediate levels. A significant correlation between sIL-6R alpha concentration and total number of leukocytes was observed in SF.

Conclusion: Elevated levels of sIL-6R alpha were found in serum, likely to result from a marked release by hepatocytes in vitro. That levels are higher in inflammatory SF may be due in part to release by inflammatory cells in situ.