NET formation is involved in de-escalation therapy in sepsis.
To elucidate the relationship between NET formation and organ injury in
the late stage of sepsis, we performed histological and
immunohistochemical staining of samples from the lung, intestine, and
liver. The damage in the sepsis groups was significantly worse than that
in the sham group, and compared with escalation therapy, de-escalation
therapy reduced intra-alveolar hemorrhage, interstitial edema, and acute
inflammatory cell infiltration.
The
lung injury score in the de-escalation group was lower than that in the
escalation group. In the liver and intestine samples, we compared the
results of the histological and immunohistochemical analyses of citH3
and
apoptosis
(Fig 6A-C). The injury, injury scores, and apoptosis levels were closely
associated with citH3 in the liver and intestine samples of those
groups. The de-escalation group had milder liver and intestine injuries
and lower NETs than the escalation group. Finally, the survival rates
were calculated in the four groups. Compared with the control,
antibiotic administration was more effective, but de-escalation therapy
in the CLP mice did not lead to significantly higher survival than
escalation therapy (p=0.051, Fig 6D).
All the data suggested that de-escalation antibiotic therapy positively
regulates immune function by increasing NET formation to maximize the
capacity to kill bacteria during the early stage of sepsis and
negatively regulates immune function by decreasing NET formation to
minimize the associated overwhelming and excessive tissue injury during
the late stage of sepsis.