Effective treatment of the acute systemic inflammatory response associated with
sepsis is lacking, but likely will require new ways to rebalance dysregulated immune responses. One challenge is that human
sepsis often is diagnosed too late to reduce the hyperinflammation of early
sepsis. Another is that the sequential response to
sepsis inflammation rapidly generates an adaptive and immunosuppressive state, which by epigenetic imprint may last for months or years. Emerging data support that the immunosuppressive phase of
sepsis can both directly reprogram gene expression of circulating and tissue cells, and disrupt development and differentiation of myeloid precursor cells into competent immunocytes. We recently reported that adoptive transfer of bone marrow CD34(+) cells into mice after
sepsis induction by cecal
ligation and
puncture significantly improves late-
sepsis survival by enhancing bacterial clearance through improved neutrophil and macrophage phagocytosis. That study, however, did not examine whether CD34(+) transfer can modify noninfectious acute systemic inflammatory responses. Here, we report that CD34(+) cell transfer mice that have survived late
sepsis also resist lethal
lipopolysaccharide (LPS)-induced inflammatory
shock (88% lived vs 0% of naive mice). The CD34(+) cell-recipient survivor mice administered LPS had globally reduced levels of circulating inflammatory mediators compared with naive mice, but their peritoneal and bone marrow-derived macrophages (BMDMs), unlike those from naïve mice, remained LPS responsive ex vivo. We further found that CD34(+) cell transfer into LPS-challenged naïve mice had diminished immunosuppression, as assessed by ex vivo responses of peritoneal and BMDMs to LPS challenge. We conclude that CD34(+) cell adoptive transfer rebalances dysregulated immune responses associated with
sepsis and
endotoxin shock.