C23, an oligopeptide derived from cold-inducible RNA-binding protein, suppresses inflammation and reduces lung injury in neonatal sepsis
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In brief
In brief
This preclinical study demonstrates that C23, a peptide inhibitor of cold-inducible RNA-binding protein (CIRP), significantly reduces systemic inflammation and lung injury in a neonatal mouse sepsis model. Treatment with C23 decreased proinflammatory cytokines IL-6 and IL-1β by up to 78% and reduced histologic lung injury scores, suggesting potential therapeutic application in neonatal sepsis management.
Written by the GCMD Library team from the article.
Introduction
Neonatal sepsis remains a leading cause of infant mortality. Cold-inducible RNA binding protein (CIRP) is an inflammatory mediator that induces TNF-α production in macrophages. C23 is a CIRP-derived peptide that blocks CIRP from binding its receptor. We therefore hypothesized that treatment with C23 reduces systemic inflammation and protects the lungs in neonatal sepsis.
Methods
Sepsis was induced in C56BL/6 mouse pups (5–7 days) by intraperitoneal injection of adult cecal slurry (0.525 mg/g body weight, LD100). One hour later pups received retroorbital injection of C23 (8 mg/kg) or vehicle (normal saline). Ten hours after sepsis induction, blood and tissues were collected for analysis.
Results
C23 treatment resulted in a 58% and 69% reduction in serum levels of proinflammatory cytokines IL-6 and IL-1β, respectively, and a 40% and 45% reduction of AST and LDH, as compared to vehicle-treated septic pups. In the lungs, C23 treatment reduced expression of cytokines IL-6 and IL-1β by 78% and 74%. In addition, the mRNA level of neutrophil chemoattractants KC and MIP-2 was reduced by 84% and 74%, respectively. These results corresponded to a reduction in histologic lung injury score. Vehicle-treated pups scored 0.49 ± 0.19, while C23 treatment reduced scores to 0.29 ± 0.12 (p