Interleukin-1ß Protection Against Experimental Sepsis in Mice.

ABSTRACT

The inflammatory response involving interleukin-1ß (IL-1ß) 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-1ß 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-1ß 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-1ß were adoptively transferred into CLP mice. GFP+-C57BL/6 parabiosis models were established. Serum IL-1ß 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-1ß treatment improved the survival of sepsis and increased the numbers of BMCs and liver immune cells in septic mice. Moreover, IL-1ß stimulation increased the number and the percentage of CD11c-CD45RBhigh DCs in septic BM and liver. Adoptive transfer of septic BMCs, liver immune cells, and CD11c-CD45RBhigh DCs treated with IL-1ß into CLP mice attenuated sepsis. IL-1ß triggered the redistribution of CD11c-CD45RBhigh DCs as well as BMCs in parabiosis models. IL-1ß protects against sepsis by stimulating local proliferation and differentiation of BMCs into CD11c-CD45RBhigh DCs at immune organs and non-immune organs.