Inhibition of the production of proinflammatory cytokines and immunoglobulins by interleukin-4 in an ex vivo model of rheumatoid synovitis

Arthritis Rheum. 1992 Aug;35(8):874-83. doi: 10.1002/art.1780350805.


Objective: To assess the spontaneous production of proinflammatory cytokines and immunoglobulins in rheumatoid arthritis (RA) synovitis and modulation by interleukin-4 (IL-4).

Methods: We developed an ex vivo model of RA synovitis using pieces of RA synovium, and have studied the regulation of the production of IL-1 beta, IL-6, tumor necrosis factor alpha (TNF alpha), IgM, and IgG.

Results: Spontaneous production of proinflammatory cytokines in vitro was active, with prolonged cytokine gene transcription and translation. IL-6 was produced at higher levels than either IL-1 beta or TNF alpha, and explants produced more IgG than IgM. In contrast, IL-4 and interferon-gamma were undetectable. When pieces of synovium were incubated in the presence of IL-4, reduction of spontaneous proinflammatory cytokine and Ig production was observed.

Conclusion: These results extend the observations of the antiinflammatory properties of IL-4 to an ex vivo situation, and provide the rationale for the clinical use of IL-4 in RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism*
  • Base Sequence
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Female
  • Humans
  • Immunoglobulin G / genetics
  • Immunoglobulin G / metabolism
  • Immunoglobulin M / genetics
  • Immunoglobulin M / metabolism
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism*
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Interleukin-4 / pharmacology*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Synovial Membrane / chemistry
  • Synovial Membrane / metabolism
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunoglobulins
  • Interleukin-1
  • Interleukin-6
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-4