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Journal of Immunology Research
Volume 2017, Article ID 9570129, 9 pages
Review Article

TNF Tolerance in Monocytes and Macrophages: Characteristics and Molecular Mechanisms

Institute of Clinical Chemistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany

Correspondence should be addressed to René Huber; ed.revonnah-hm@ener.rebuh and Korbinian Brand; ed.revonnah-hm@nainibrok.dnarb

Received 27 July 2017; Accepted 25 September 2017; Published 8 November 2017

Academic Editor: Kebin Hu

Copyright © 2017 René Huber et al. 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.


Tumor necrosis factor (TNF) tolerance in monocytes and macrophages means that preexposure to TNF reduces the sensitivity in these cells to a subsequent restimulation with this cytokine. Differential effects arise following preincubation with both low and high doses of TNF resulting in absolute as well as induction tolerance affecting specific immunologically relevant gene sets. In this review article, we summarize the relevance of TNF tolerance in vivo and the molecular mechanisms underlying these forms of tolerance including the role of transcription factors and signaling systems. In addition, the characteristics of cross-tolerance between TNF and lipopolysaccharide (LPS) as well as pathophysiological aspects of TNF tolerance are discussed. We conclude that TNF tolerance may represent a protective mechanism involved in the termination of inflammation and preventing excessive or prolonged inflammation. Otherwise, tolerance may also be a trigger of immune paralysis thus contributing to severe inflammatory diseases such as sepsis. An improved understanding of TNF tolerance will presumably facilitate the implementation of diagnostic or therapeutic approaches to more precisely assess and treat inflammation-related diseases.