A cold-inducible RNA-binding protein (CIRP)-derived peptide attenuates inflammation and organ injury in septic mice.

Cold-inducible RNA-binding protein (CIRP) is a novel sepsis inflammatory mediator and C23 is a putative CIRP competitive inhibitor. Therefore， we hypothesized that C23 can ameliorate sepsis-associated injury to the lungs and kidneys. First， we confirmed that C23 dose-dependently inhibited TNF-α release， IκBα degradation， and NF-κB nuclear translocation in macrophages stimulated with CIRP. Next， we observed that male C57BL/6 mice treated with C23 (8 mg/kg BW) at 2 h after cecal ligation and puncture (CLP) had lower serum levels of LDH， ALT， IL-6， TNF-α， and IL-1β (reduced by ≥39%) at 20 h after CLP compared with mice treated with vehicle. C23-treated mice also had improved lung histology， less TUNEL-positive cells， lower serum levels of creatinine (34%) and BUN (26%)， and lower kidney expression of NGAL (50%) and KIM-1 (86%). C23-treated mice also had reduced lung and kidney levels of IL-6， TNF-α， and IL-1β. E-selectin and ICAM-1 mRNA was significantly lower in C23-treated mice. The 10-day survival after CLP of vehicle-treated mice was 55%， while that of C23-treated mice was 85%. In summary， C23 decreased systemic， lung， and kidney injury and inflammation， and improved the survival rate after CLP， suggesting that it may be developed as a new treatment for sepsis.