Synovial fluid from patients with rheumatoid arthritis inhibits neutrophil apoptosis: role of adenosine and proinflammatory cytokines

Rheumatology (Oxford). 2002 Nov;41(11):1249-60. doi: 10.1093/rheumatology/41.11.1249.


Objective: In synovial fluid (SF) from patients with rheumatoid arthritis (RA), neutrophils are exposed to proinflammatory mediators endowed with either anti-apoptotic or pro-apoptotic properties. We investigated neutrophil apoptosis in the presence of SF from 11 RA patients.

Methods: SF was obtained from affected knees of 11 patients with RA. Human neutrophil apoptosis was evaluated by light microscopic examination and flow-cytometric analysis of annexin V binding. Immune complex-induced neutrophil activation was evaluated as superoxide anion production. Adenosine levels in SF were detected by chromatographic analysis and cytokine levels were studied by enzyme-linked immunosorbent assay.

Results: Spontaneous and immune complex-triggered neutrophil apoptosis was reduced by SF from eight out of 11 patients. Immune complex-induced neutrophil activation was unaffected by SF. The cytokines tested had no role in promoting the anti-apoptotic activity of SF. On the contrary, the anti-apoptotic activity of SF was found to depend on the presence of adenosine. Adenosine levels detected in the various samples of SF correlated significantly with the anti-apoptotic activity of the fluids and with the number of apoptotic neutrophils detected in the articular exudate.

Conclusion: The microenvironment of rheumatoid SF is a proinflammatory milieu responsible for the in loco persistence of activated and long-surviving neutrophils. Adenosine plays a crucial role in this phenomenon, which is related to anti-apoptotic activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism*
  • Adult
  • Apoptosis / drug effects*
  • Arthritis, Rheumatoid / physiopathology*
  • Cells, Cultured
  • Culture Media
  • Cytokines / metabolism*
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Interleukin-15 / pharmacology
  • Interleukin-2 / pharmacology
  • Interleukin-8 / pharmacology
  • Knee Joint
  • Male
  • Middle Aged
  • Neutrophils / drug effects*
  • Neutrophils / physiology*
  • Sensitivity and Specificity
  • Synovial Fluid / chemistry*
  • Synovial Fluid / cytology*
  • Tumor Necrosis Factor-alpha / pharmacology


  • Culture Media
  • Cytokines
  • Interleukin-15
  • Interleukin-2
  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Adenosine