Interleukin 4, but not interleukin 10, regulates the production of inflammation mediators by rheumatoid synoviocytes

Cytokine. 1995 Feb;7(2):176-83. doi: 10.1006/cyto.1995.1024.

Abstract

Rheumatoid synovitis is characterized by increased activation and proliferation of synoviocytes, which are an important source of cytokines. The role of Interleukin 4 (IL-4) and IL-10 on the production of mediators of inflammation by rheumatoid synoviocytes was studied herein. While IL-4 weakly affected the spontaneous PGE2 production, it strongly inhibited its production when cells were stimulated with IL-1 beta and TNF-alpha. IL-4 decreased by 60% to 80% the spontaneous and the IL-1 beta or TNF-alpha induced synthesis of GM-CSF. In contrast, IL-4 enhanced the spontaneous (2.6-fold), and to a lower extent (1.3-1.8-fold), the cytokine stimulated production of IL-6. This induction was not due to a passive release of pre-synthesized IL-6, since IL-4 increased the level of IL-6 mRNA expression induced by IL-1 beta. The D50 was 5 U/ml of IL-4 for both the stimulation of IL-6 synthesis and the inhibition of GM-CSF production. Kinetic studies of the action of IL-4 revealed a rapid and sustained inhibition of GM-CSF production, and a late increase of IL-6 secretion. By contrast, IL-10 had no effect on the production of either IL-6 or GM-CSF by synoviocytes. Thus, by inhibiting synoviocyte proliferation and inhibiting their secretion of PGE2 and GM-CSF, IL-4 displays on synoviocytes a series of biological effects which complements its anti-inflammatory properties on monocytes.

Publication types

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

MeSH terms

  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / physiopathology*
  • Cells, Cultured
  • Dinoprostone / biosynthesis*
  • Gene Expression / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis*
  • Humans
  • Inflammation
  • Interleukin-10 / pharmacology*
  • Interleukin-4 / pharmacology*
  • Interleukin-6 / biosynthesis*
  • Kinetics
  • RNA, Messenger / biosynthesis
  • Recombinant Proteins / pharmacology
  • Synovial Membrane / immunology
  • Synovial Membrane / physiopathology*
  • Time Factors

Substances

  • Interleukin-6
  • RNA, Messenger
  • Recombinant Proteins
  • Interleukin-10
  • Interleukin-4
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Dinoprostone