CONCENTRATIONS AND ORIGINS OF SOLUBLE INTERLEUKIN-6 RECEPTOR-ALPHA INSERUM 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 di fferent rheumatic diseases, and to analyze its cellular origin compare d to IL-6. Methods, IL-6 and sIL-6R alpha concentrations were measured in sera, SF, and culture supernatants of different cell types using s pecific sandwich ELISA. Results. IL-6 levels were significantly higher (30 to 1000-fold) in SF than in sera, and higher in inflammatory arth ropathies such as rheumatoid arthritis (RA), chondrocalcinosis, and go ut than in osteoarthritis (OA). sIL-6R alpha levels in SF from patient s 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 sma ller. In contrast, sIL-6R alpha concentrations did not differ signific antly between the sera of healthy donors and patients. sIL-6R alpha le vels 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 hep atocytes but not by structural cells of the joint (chondrocytes, synov iocytes, fibroblasts, and endothelial cells). Polymorphonuclear cells and mononuclear cells released intermediate levels. A significant corr elation between sIL-6R alpha concentration and total number of leukocy tes was observed in SE Conclusion, Elevated levels of sIL-6R alpha wer e found in serum, likely to result from a marked release by hepatocyte s in vitro. That levels are higher in inflammatory SF may be due in pa rt to release by inflammatory cells in situ.