- Meeting abstract
- Open Access
- Published:
Interfering With Inflammation During Cell-Cell Interaction
Arthritis Research & Therapyvolume 1, Article number: S31 (1999)
Full text
In chronic inflammatory diseases, immunocompetent infiltrating cells are in the vicinity of or in direct contact with resident cells, representing the principal pathway for stimulating proinflammatory and prodestructive cytokines and metalloproteinases (MMPs). During the direct contact between activated T lymphocytes and fibroblasts or mesenchymal-derived cells, such as synovial cells, membrane-bound TNFα and IL-1 are the principal cytokines involved in MMP production by fibroblasts. Therefore, therapies involving Ab to TNFα (ie soluble receptors or antibodies) and to IL-1 (ie IL-1Ra or soluble IL-1 receptor type II) are perfectly rational. In the direct contact between activated TL and monocyte-macrophages (Mφ), TL stimulated by mAb to CD3 favor the production of MMP-1 over that of TIMP-1, with Th1 cell clones inducing preferentially the expression of IL-1β and TNFα, and Th2 that of IL-1Ra. The induction of cytokines and MMPs during TL/Mφ contact is partially inhibited (30-50%) by mAb to CD11 (b > c > a) and CD69. Contrary to the interaction between TL and fibroblasts, the blockade of membrane-bound TNFα and IL-1 has no effect on TL/Mφ interaction. The identification of distinct cell-surface molecules on TL driving either proinflammatory cytokines and MMP or anti-inflammatory cytokines and TIMP-1 allows the design of drugs that ensure more precise targeting of therapeutic intervention. Some of these recent drugs decrease cell-surface molecules on activated T cells that are involved in the induction of IL-1β (but not of IL-1Ra) on monocytes.
References
- 1.
Chizzolini C, Chicheportiche R, Songeon F, Dayer J-M: Human Th1 cells preferentially induce interleukin (IL)-1beta while Th2 cells induce IL-1 receptor antagonist production upon cell/cell contact with monocytes. Eur J Immunol. 1997, 27: 171-177.
- 2.
Coclet-Ninin J, Dayer J-M, Burger D: Interferon-beta not only inhibits interleukin-1beta and tumor necrosis factor-alpha but stimulates interleukin-1 receptor antagonist production in human peripheral blood mononuclear cells. Eur Cytokine Netw. 1997, 4: 345-349.
- 3.
Loetscher P, Uguccioni M, Bordoli L, et al: CCR5 is characteristic of Th1 lymphocytes. Nature. 1998, 391: 344-345. 10.1038/34814.
- 4.
Rezzonico R, Burger D, Dayer J-M: Direct contact between T lymphocytes and human dermal fibroblasts or synoviocytes down-regulates types I and III collagen production via cell-associated cytokines. J Biol Chem. 1998, 273: 18720-18728. 10.1074/jbc.273.30.18720.
- 5.
Burger D, Rezzonico R, Li J-M, et al: Imbalance between interstitial collagenase (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in synoviocytes and fibtroblasts upon direct contact with stimulated T lymphocytes : involvement of membrane-associated cytokines. Arthritis Rheum. 1998, 41: 1748-1759. 10.1002/1529-0131(199810)41:10<1748::AID-ART7>3.3.CO;2-V.
- 6.
Déage V, Burger D, Dayer J-M: Exposure of T lymphocytes to leflunomide but not to dexamethasone favors the production by monocytic cells of interleukin-1 receptor antagonist and the tissue inhibitor of metalloproteinases-1 over that of interleukin-1beta and metalloproteinases. Eur Cytokine Netw. 1998, 9: 663-668.
- 7.
Burger D, Dayer J-M: Interactions between T cell plasma membranes and monocytes. In T Cells in Arthritis. Edited by Miossec P, van der Berg WB, Firestein GS. Basel: Birkhäuser. 1998, : 111-128.
Author information
Affiliations
Rights and permissions
About this article
Published
DOI
Keywords
- Direct Contact
- Chronic Inflammatory Disease
- Synovial Cell
- Soluble Receptor
- Resident Cell
