Abatacept modulates proinflammatory macrophage responses upon cytokine-activated T cell and Toll-like receptor ligand stimulation

Wenink, M.H., Santegoets, K.C.M., Platt, A.M., van den Berg, W.B., van Riel, P.L.C.M., Garside, P. , Radstake, T.R.D.J. and McInnes, I.B. (2012) Abatacept modulates proinflammatory macrophage responses upon cytokine-activated T cell and Toll-like receptor ligand stimulation. Annals of the Rheumatic Diseases, 71(1), pp. 80-83. (doi: 10.1136/annrheumdis-2011-200348) (PMID:21908454)

Abstract

<p>Objectives: We investigated whether Abatacept might reduce proinflammatory cytokine production by macrophages upon contact with cytokine activated T cells and/or stimulation with TLR ligands.</p> <p>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.</p> <p>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.</p> <p>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.</p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain and Garside, Professor Paul and Platt, Dr Andrew
• Authors: Wenink, M.H., Santegoets, K.C.M., Platt, A.M., van den Berg, W.B., van Riel, P.L.C.M., Garside, P., Radstake, T.R.D.J., and McInnes, I.B.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Annals of the Rheumatic Diseases
• Publisher: B M J Group
• ISSN: 0003-4967
• Published Online: 08 September 2011