Volume 6 Supplement 3

Global Arthritis Research Network (GARN): 4th World Congress on Arthritis in Montreal

Open Access

Different molecules at the surface of stimulated T cells induce IL-1α, tumor necrosis factor and IL-1 receptor antagonist in human monocytes

  • D Burger1,
  • N Molnarfi1,
  • L Gruaz1 and
  • J-M Dayer1
Arthritis Res Ther20046(Suppl 3):70

https://doi.org/10.1186/ar1426

Published: 13 September 2004

An imbalance in cytokine homeostasis is thought to play an important part in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis and multiple sclerosis. We demonstrated that T cells might exert a pathological effect through direct cellular contact with monocyte-macrophages, inducing a massive upregulation of IL-1 and tumor necrosis factor (TNF). More recently, we showed that this mechanism, likely to be of relevance to chronic inflammation, is specifically inhibited by high-density lipoproteins (HDL). Like many other stimuli besides proinflammatory cytokines, the contact-mediated activation of monocytes induces the production of cytokine inhibitors such as IL-1 receptor antagonist (IL-1Ra). We observed that HDL inhibited the production of IL-1β and TNF but not that of IL-1Ra induced in monocytes after activation by membranes isolated from stimulated T cells to mimic cellular contact. This was also observed in peripheral blood mononuclear cells stimulated by either phytohemagglutinin or tetanus toxoid, in which the presence of isolated HDL inhibited the production of IL-1β and TNF while that of IL-1Ra remained unchanged. This effect was confirmed by activating isolated monocytes with CHAPS-solubilized membranes from stimulated T cells, suggesting that HDL interacted with a specific factor expressed at the surface of T cells and not unspecifically with isolated membranes. Similarly, IL-1Ra mRNA expression was not inhibited, contrary to IL-1β and TNF mRNA. This demonstrates that different molecules at the surface of stimulated HUT-78 cells are involved in the induction of IL-1β, TNF and IL-1Ra in monocytes, IL-1β and TNF being activated by one or more HDL-specific ligands. Separation of CHAPS-solubilized membrane molecules by liquid isoelectric focusing revealed two activity peaks: one activating IL-1β, TNF and IL-1Ra production; the other inducing the production of IL-1Ra in the absence of IL-1β and TNF. Thus different factors are expressed at the surface of stimulated T cells that are differently affected by HDL and differentially trigger the production of proinflammatory and antiinflammatory factors.

Authors’ Affiliations

(1)
Division of Immunology & Allergy (Hans Wilsdorf Laboratory), University Hospital

Copyright

© The Author(s) 2004

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