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Interfering With Inflammation During Cell-Cell Interaction

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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.


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Dayer, JM. Interfering With Inflammation During Cell-Cell Interaction. Arthritis Res Ther 1 (Suppl 1), S31 (1999).

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