Schroeder, Martina and Meisel, Christian and Buhl, Katharina and Profanter, Nina and Sievert, Nadine and Volk, Hans-Dieter and Grutz, Gerald (2003) Different Modes of IL-10 and TGF-β to Inhibit Cytokine-Dependent IFN-γ Production: Consequences for Reversal of Lipopolysaccharide Desensitization. Journal of Immunology, 170. pp. 5260-5267. ISSN 0022-1767

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Abstract

LPS hyporesponsiveness is characterized by a diminished production of proinflammatory cytokines which can be caused by pretreatment with either LPS (=LPS desensitization) or the combination of the anti-inflammatory cytokines IL-10 and TGF-β. However, the resulting hyporesponsive states differ regarding their reversibility by the IFN-γ-inducing cytokine IL-12. Therefore, we aimed at studying the reasons for this differential IL-12 responsiveness of IFN-γ-producing cells and its consequences for LPS hyporesponsiveness in more detail. In an in vitro IL-12/IL-18 responsiveness model, we demonstrated that IL-10, if permanently present, does not directly inhibit IL-12/IL-18 responsiveness in T/NK cells but indirectly interferes with IFN-γ production in the presence of monocytes. In contrast, TGF-β acted directly on IFN-γ-producing cells by interfering with IL-12/IL-18 responsiveness. After removal of IL-10 but not of TGF-β, LPS hyporesponsiveness can be reverted by IL-12/IL-18. Consequently, the addition of recombinant TGF-β during LPS desensitization rendered PBMCs hyporesponsive to a reversal by IL-12/IL-18. Our data suggest that the persistence of IL-10 and the presence of TGF-β determine the level of IFN-γ inhibition and may result in different functional phenotypes of LPS desensitization and LPS hyporesponsiveness in vitro and in vivo.

Item Type:	Article
Keywords:	Different Modes; IL-10; TGF-β; Inhibit; Cytokine-Dependent; IFN-γ; Production; Reversal; Lipopolysaccharide; Desensitization;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	12668
Identification Number:	https://doi.org/10.4049/jimmunol.170.10.5260
Depositing User:	Martina Schroeder
Date Deposited:	31 Mar 2020 12:41
Journal or Publication Title:	Journal of Immunology
Publisher:	American Association of Immunologists
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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