1. IL-1R1 blockade attenuates liver injury through inhibiting the recruitment of myeloid-derived suppressor cells in sepsis.
- Author
-
Luo M, Wang H, Liu K, Liu M, Tan S, Zhu Y, and Zhang H
- Subjects
- Animals, CD8-Positive T-Lymphocytes, Humans, Interleukin 1 Receptor Antagonist Protein pharmacology, Interleukin 1 Receptor Antagonist Protein therapeutic use, Liver, Mice, Mice, Inbred C57BL, Myeloid-Derived Suppressor Cells, Receptors, Interleukin-1 Type I metabolism, Sepsis drug therapy
- Abstract
Myeloid-derived suppressor cells (MDSCs) mobilize and migrate from bone marrow to peripheral tissues or immune organs, which is associated with poor prognosis in sepsis. Intervention of MDSCs might be a potential target for the effective treatment of sepsis. In the present study, we demonstrated that IL-1R1 blockade with either recombinant human IL-1R antagonist Anakinra or IL-1R1 deficiency had a protective effect on the liver injury in septic mice. The possible mechanism was that Anakinra treatment and IL-1R1 knockout inhibited the migration of MDSCs to the liver in sepsis, thus attenuating the immune suppression of MDSCs on effector T cells characterized with the decrease in proportion of CD4
+ and CD8+ T cells. Furthermore, the switch from pro-inflammatory M1 macrophage to anti-inflammatory M2 phenotype and the ability of bacterial clearance in the liver of septic mice were enhanced obviously by Anakinra and IL-1R1 deficiency, which contributes to the attenuated liver injury. Taken together, these findings provide new ideas for revealing the relationship between IL-1R1 and MDSCs in sepsis, thereby providing a potentially effective target for ameliorating septic liver injury., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2022
- Full Text
- View/download PDF