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Neutrophil extracellular traps (NETs) exacerbate severity of infant sepsis

Critical Care Apr 14, 2019

Colón DF, et al. - Researchers investigated the role of neutrophil extracellular traps (NETs) in pediatric sepsis. For this purpose, they induced sepsis via intraperitoneal (i.p.) injection of bacteria suspension or lipopolysaccharide (LPS) in infant (2 weeks old) and adult (6 weeks old) mice and measured neutrophil infiltration, bacteremia, organ injury, and plasma levels of cytokine, NETs, and DNase. They found significantly higher levels of NETs in infant C57BL/6 mice subjected to sepsis or LPS-induced endotoxemia vs the adult mice. Moreover, increased organ injury and production of inflammatory cytokines were seen along with this outcome, as compared to the adult mice. Elevated expression of Padi4 (Peptidyl arginine deiminase 4) and histone H3 citrullination in the neutrophils was seen in relation to increased NETs. A remarkable reduction in sepsis was observed when infant septic mice were treated with rhDNase or a PAD-4 inhibitor. High levels of NETs were detected among pediatric septic patients, and there was a positive correlation of the severity of pediatric sepsis with the level of NETs.
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