Route of monocyte differentiation determines their cytokine production profile: CD40 ligation induces interleukin 10 expression.

Andrew D. Foey*, Marc Feldmann, Fionula M. Brennan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Interleukin 10 is a potent anti-inflammatory and immunomodulatory cytokine. Little is known regarding its induction in monocytes/macrophages, however LPS, a reproducible trigger of IL-10, is augmented by direct contact with T cells. In this context, the role of CD40-ligation is investigated. In the rheumatoid synovium, IL-10 is produced by tissue macrophages. Monocytes primed with M-CSF, a cytokine present in rheumatoid joints, produced IL-1beta, TNF-alpha and IL-10 upon CD40-ligation at an IL-1: TNF-alpha: IL-10 ratio of 10:0.5:1. IFN-gamma-primed monocytes, however, predominantly produced TNF-alpha and IL-1beta. Both differentiated monocytes display an endogenous IL-10 activity regulatable by CD40 stimulation. Additionally, these monocytes display differential control by exogenous and endogenous IL-1 and TNF-alpha. M-CSF-primed monocyte IL-10 production was dependent on endogenous TNF-alpha and, to a lesser extent, IL-1, whereas IFN-gamma-primed monocytes were partially dependent on endogenous IL-1. The addition of exogenous IL-1 augments CD40 induced IL-10 production by IFN-gamma-primed monocytes. These data indicate that CD40 ligation regulates cell contact mediated macrophage IL-10 and that the route of differentiation determines the cytokine profile.
Original languageEnglish
Pages (from-to)1496-1505
Number of pages0
JournalCytokine
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 2000

Keywords

  • CD40 Antigens
  • Cell Differentiation
  • Cell Membrane
  • Coculture Techniques
  • Cytokines
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interferon-gamma
  • Interleukin-1
  • Interleukin-10
  • Leukocytes
  • Mononuclear
  • Lipopolysaccharides
  • Macrophage Colony-Stimulating Factor
  • Macrophages
  • Monocytes
  • Phenotype
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tumor Necrosis Factor-alpha

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