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.


CONCLUSIONS
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.
Desgeorges
A
A
Division de Rhumatologie, Hôpital Universitaire, Geneva, Switzerland.
Gabay
C
C
Silacci
P
P
Novick
D
D
Roux-Lombard
P
P
Grau
G
G
Dayer
J M
JM
Vischer
T
T
Guerne
P A
PA
D015703:Antigens, CD / Q000378:metabolism*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism*; D019947:Receptors, Interleukin-6; D012216:Rheumatic Diseases / Q000097:blood*; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism*
D015703:Antigens, CD; D006131:Growth Inhibitors; D015850:Interleukin-6; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6