Levels of circulating tumor necrosis factor alpha and interleukin-6 in patients with rheumatoid arthritis. Relationship to serum levels of hyaluronan and antigenic keratan sulfate

Arthritis Rheum. 1993 Apr;36(4):490-9. doi: 10.1002/art.1780360409.


Objective: To measure serum levels of tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) in patients with rheumatoid arthritis (RA) and age-matched control subjects and to study how these correlate with serum levels of hyaluronan (HA) and antigenic keratan sulfate (KS) and other biochemical as well as clinical indicators of disease activity.

Methods: Immunoassays were used to measure levels of TNF alpha, IL-6, HA, and antigenic KS in the serum of 35 patients with RA and a group of age- and sex-matched control subjects. Clinical disease activity in the RA group was assessed using the Lansbury index. Drug intake was recorded and the erythrocyte sedimentation rate, and levels of fibrinogen, creatinine, bilirubin, alkaline phosphatase, lactate dehydrogenase, and aminotransferase were measured.

Results: Serum levels of TNF alpha, IL-6, and HA were significantly higher in the RA population than in the control group. In patients with RA, serum levels of HA correlated positively with serum levels of TNF alpha and with clinical joint scores, but only weakly with other laboratory parameters of inflammation. Serum levels of antigenic KS correlated negatively with levels of circulating TNF alpha, but much more weakly with other clinical and biochemical parameters of disease activity.

Conclusion: These in vivo data support in vitro studies which have shown that TNF alpha is a potent stimulator of HA synthesis by synovial lining cells. The results strengthen the contention that serum HA may be a unique marker of synovial involvement and inflammation, rather than of only inflammation, in RA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens / blood*
  • Arthritis, Rheumatoid / blood*
  • Blood Sedimentation
  • C-Reactive Protein / analysis
  • Female
  • Fibrinogen / analysis
  • Humans
  • Hyaluronic Acid / blood*
  • Interleukin-6 / blood*
  • Keratan Sulfate / immunology*
  • Kidney / physiology
  • Liver / physiology
  • Lymphokines / blood
  • Male
  • Middle Aged
  • Tumor Necrosis Factor-alpha / analysis*


  • Antigens
  • Interleukin-6
  • Lymphokines
  • Tumor Necrosis Factor-alpha
  • Fibrinogen
  • Hyaluronic Acid
  • C-Reactive Protein
  • Keratan Sulfate