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 language | English |
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Pages (from-to) | 1496-1505 |
Number of pages | 0 |
Journal | Cytokine |
Volume | 12 |
Issue number | 10 |
DOIs | |
Publication status | Published - 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