De-escalation antibiotic therapy alleviates NET-associated organ
injury and inflammation in CLP model.
Considering the role of NETs in the progression of sepsis,
NET-associated organ injury was assessed. In the early stage of sepsis,
both the levels of AST and serum creatinine were significantly lower in
the de-escalation group (imipenem for 3 days) than in the escalation
group (ceftriaxone for 3 days) and the control group (Fig 3A-B).
However, when DNase I was administered to the escalation group for 3
days, there was no significant difference between the levels of AST and
serum creatinine in this group, although these levels were lower than
those in the control groups. Next, we measured the inflammatory
response. Consistent with the levels of AST and serum creatinine, the
levels of serum IL-6, IL-10, and IFN-γ were lower in the de-escalation
group than in the other groups (Fig 3C-E). Interestingly, the level of
MCP-1 was lower in the escalation group. Then, we used DNase I in the
de-escalation group. The levels of all the cytokines were elevated, and
the level of MCP-1 was decreased (Fig 3F).
Next, we measured these factors in the late stage of sepsis. First, we
measured the AST, ALT, LDH, and serum creatinine levels to evaluate
organ injury. There were varying degrees of damage in the sepsis group
compared with the sham group, and all the serum biochemical values were
lower in the de-escalation group than in the escalation group (Fig
4A-D). The levels of the cytokines IL-6, IL-10, IFN-γ, MIP-2 and MCP-1
were consistent with the biochemical values in the two groups (Fig
5A-F).
These findings suggested that NETs exert a protective role in the early
stage of sepsis, which can alleviate organ injury and the inflammatory
response, and reduced NET production is beneficial to septic mice in the
late stage.