IL-1R1 blockade attenuates liver injury through inhibiting the recruitment of myeloid-derived suppressor cells in sepsis

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. (C) 2022 The Author(s). Published by Elsevier Inc.

Automated summary

This study demonstrates that blockade of IL-1R1 has a protective effect on liver injury in septic mice. Anakinra treatment and IL-1R1 deficiency inhibit the migration of MDSCs to the liver in sepsis, attenuating the immune suppression of MDSCs on effector T cells. Furthermore, IL-1R1 blockade promotes the switch from pro-inflammatory M1 macrophage to anti-inflammatory M2 phenotype and enhances bacterial clearance in the liver, contributing to the attenuation of liver injury.