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Antibodies 2015, 4(2), 123-140; doi:10.3390/antib4020123

Reverse Signaling Contributes to Control of Chronic Inflammation by Anti-TNF Therapeutics

1
Institute of Medical Biology, University of Szeged, 6720, Szeged, Hungary
2
Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090, Vienna, Austria
*
Author to whom correspondence should be addressed.
Academic Editor: Olaf Maier
Received: 17 February 2015 / Revised: 11 May 2015 / Accepted: 29 May 2015 / Published: 9 June 2015
(This article belongs to the Special Issue TNF in the Regulation of Immune Cells)
View Full-Text   |   Download PDF [1262 KB, uploaded 9 June 2015]   |  

Abstract

Anti-tumor necrosis factor (TNF) monoclonal antibodies and TNF receptor ectodomain fusion protein are in clinical use to neutralize circulating TNF and ameliorate symptoms of many autoimmune diseases and pathological conditions with chronic inflammation. In this paper we present data to prove that reverse signaling, elicited by agonist molecules interacting with the membrane-bound TNF of myeloid cells, significantly contributes to the therapeutic effect of these anti-TNF medicines. Interaction of agonist monoclonals with cell surface TNF significantly attenuates the expression of pro-inflammatory cytokines and induces changes in the production of extracellular and intracellular signaling molecules. This phenomenon is not dependent on the Fc portion of antibodies as Fab constructs are as efficient as full antibody molecules. View Full-Text
Keywords: autoimmune; monoclonal antibodies; inflammation; macrophage; reverse signal; tumor necrosis factor (TNF); TNF receptor autoimmune; monoclonal antibodies; inflammation; macrophage; reverse signal; tumor necrosis factor (TNF); TNF receptor
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Sipos, O.; Török, A.; Kalic, T.; Duda, E.; Filkor, K. Reverse Signaling Contributes to Control of Chronic Inflammation by Anti-TNF Therapeutics. Antibodies 2015, 4, 123-140.

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