Interleukin-1β Protection Against Experimental Sepsis in Mice

The inflammatory response involving interleukin-1β (IL-1β) has been thought to play an important role in the development of late-phase sepsis. However, in this study, we wanted to explore the possibility of using IL-1β to improve the prognosis of sepsis by triggering local differentiation of bone marrow cells (BMCs) into regulatory dendritic cells (DCs) in vivo, thereby reversing the immune paralysis in late-phase sepsis. Sepsis mouse models were induced by cecal ligation and puncture (CLP) and lethal Escherichia coli O18 infection. Mice were injected intraperitoneally with IL-1β after CLP and after the lethal infection. Septic BMCs and liver immune cells were isolated at 0, 3, 6, 9, and 14 days post-CLP. BMCs and liver cells isolated from septic mice treated with IL-1β were adoptively transferred into CLP mice. GFP⁺-C57BL/6 parabiosis models were established. Serum IL-1β levels were determined by enzyme-linked immunosorbent assay (ELISA) kit, and the number, ratio, and phenotype of immune cells were observed by flow cytometry. IL-1β treatment improved the survival of sepsis and increased the numbers of BMCs and liver immune cells in septic mice. Moreover, IL-1β stimulation increased the number and the percentage of CD11c^-CD45RB^high DCs in septic BM and liver. Adoptive transfer of septic BMCs, liver immune cells, and CD11c^-CD45RB^high DCs treated with IL-1β into CLP mice attenuated sepsis. IL-1β triggered the redistribution of CD11c^-CD45RB^high DCs as well as BMCs in parabiosis models. IL-1β protects against sepsis by stimulating local proliferation and differentiation of BMCs into CD11c^-CD45RB^high DCs at immune organs and non-immune organs.