title: Abatacept modulates proinflammatory macrophage responses upon cytokine-activated T cell and Toll-like receptor ligand stimulation.
abstract: OBJECTIVE
  We investigated whether Abatacept might reduce proinflammatory cytokine production by macrophages upon contact with cytokine activated T cells and/or stimulation with TLR ligands.
  
  
  METHODS
  Macrophages and cytokine stimulated T cells (Tck) were added together in the presence of Abatacept or a control Ig, with or without TLR ligands. The production of cytokines was determined by luminex.
  
  
  RESULTS
  Abatacept reduced Tck-induced production of TNFa by macrophages. Tck and TLR ligands synergistically induced the production of proinflammatory cytokines by macrophages, especially IL-12p70. The production of IL-12p70 coincided with the production of IFNg, which were both reduced in the presence of Abatacept.
  
  
  CONCLUSIONS
  Tck induce the production of TNFa by macrophages and facilitate the highly increased production of proinflammatory cytokines in the presence of TLR ligands. Abatacept was shown to potently suppress these pathways suggesting that its role may extend beyond antigen specific T cell mediated effector function.
authors: Department of Rheumatology, Nijmegen Center of Infection, Inflammation and Immunity and Nijmegen Center for Molecular Life Science, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors: M H
authors: MH
authors: Wenink
authors: K C M
authors: KC
authors: Santegoets
authors: A M
authors: AM
authors: Platt
authors: W B
authors: WB
authors: van den Berg
authors: P L C M
authors: PL
authors: van Riel
authors: P
authors: P
authors: Garside
authors: T R D J
authors: TR
authors: Radstake
authors: I B
authors: IB
authors: McInnes
mesh_terms: D000069594:Abatacept; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D008024:Ligands; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D000069594:Abatacept