Interleukin-10 functions as an antiinflammatory cytokine in rheumatoid synovium

Arthritis Rheum. 1996 Mar;39(3):386-95. doi: 10.1002/art.1780390306.


Objective: Interleukin-10 (IL-10) is an antiinflammatory cytokine that has been shown to play a role in rheumatoid arthritis (RA). We therefore investigated the effects of IL-10 on the function and phenotype of synovial fluid mononuclear cells (SFMC) derived from patients with RA. In addition, we studied the production of IL-10 in rheumatoid joints, and the role of endogenous IL-10 in the regulation of SFMC function.

Methods: The presence of IL-10 in rheumatoid joints was studied using IL-10-specific enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase- polymerase chain reaction (RT-PCR) techniques. The effects of recombinant human IL-10 or neutralizing anti-IL-10 monoclonal antibodies (MAbs) on both cytokine production and phenotype of SFMC were evaluated using cytokine-specific ELISAs and flow cytometry. The effect of IL-10 on proliferation of SFMC was determined by incorporation of tritiated thymidine.

Results: IL-10 was detected by ELISA in 22 of 23 SF samples, and was spontaneously produced by cultured SFMC. IL-10 messenger RNA was detectable in all 8 SFMC samples, as determined by RT-PCR. Neutralization of endogenously produced IL-10 by anti- IL-10 MAbs resulted in increased production of IL-1 beta, tumor necrosis factor alpha (TNF alpha), and granulocyte- macrophage colony-stimulating factor (GM-CSF) by SFMC, and in enhanced proliferation of SFMC. In particular, the production of TNFalpha was dramatically increased by anti-IL-10 MAbs. Moreover, the expression of HLA-DR molecules by SF macrophages was increased, and the expression of CD16 was decreased by anti-IL-10 MAbs. In contrast, addition of recombinant IL-10 significantly decreased the production of IL-1 beta, TNF alpha, and GM-CSF by SFMC, and decreased spontaneous and IL-2-induced proliferation of SFMC. Finally, IL-10 decreased HLA-DR expression and increased the expression of the Fc gamma receptors, CD16 and CD64, by SF macrophages.

Conclusion: These data indicate that endogenously produced IL-10 functions as an immunoregulatory molecule in rheumatoid synovium. Importantly, exogenous IL-10 has potent antiinflammatory effects on SFMC, suggesting that IL-10 may be useful in the treatment of patients with RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / immunology*
  • Antibodies, Monoclonal
  • Arthritis, Rheumatoid / immunology*
  • Base Sequence
  • Cell Division / immunology
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • HLA-DR Antigens / immunology
  • Humans
  • Interleukin-1 / biosynthesis
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Interleukin-10 / pharmacology
  • Joint Diseases / immunology
  • Macrophages / cytology
  • Macrophages / immunology
  • Macrophages / physiology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Neutralization Tests
  • Oligonucleotide Probes
  • RNA, Messenger / analysis
  • Synovial Membrane / cytology
  • Synovial Membrane / immunology*
  • Synovial Membrane / physiopathology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Cytokines
  • HLA-DR Antigens
  • Interleukin-1
  • Oligonucleotide Probes
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Granulocyte-Macrophage Colony-Stimulating Factor