Early local neutralization of CC16 in sepsisinduced ALI following blunt chest trauma leads to delayed mortality without benefitting overall survival.
Int J Mol Med
; 46(6): 2207-2215, 2020 Dec.
Article
en En
| MEDLINE
| ID: mdl-33125155
ABSTRACT
Blunt thoracic trauma (TxT) is a common injury pattern in polytraumatized patients. When combined with a secondary trigger, TxT often results in acute lung injury (ALI), which negatively affects outcomes. Recent findings suggest that ALI is caused by both local and systemic inflammatory reactions. Club cell protein (CC)16 is an antiinflammatory peptide associated with lung injury following TxT. Recently, the antiinflammatory properties of endogenous CC16 in a murine model of TxT with subsequent cecalligation and puncture (CLP) as the secondary hit were demonstrated by our group. The present study aimed to determine whether CC16 neutralization improves survival following 'doublehit'induced ALI. For this purpose, a total of 120 C57BL/6N mice were subjected to TxT, followed by CLP after 24 h. Shamoperated animals underwent anesthesia without the induction of TxT + CLP. CC16 neutralization was performed by providing a CC16 antibody intratracheally following TxT (early) or following CLP (late). Survival was assessed in 48 animals for 6 days after CLP. Sacrifice was performed 6 or 24 h postCLP to evaluate the antiinflammatory effect of CC16. The results revealed that CC16 neutralization enhanced proinflammatory CXCL1 levels, thereby confirming the antiinflammatory characteristics of CC16 in this model. Early CC16 neutralization immediately following TxT significantly prolonged survival within 60 h; however, the survival rate did not change until 6 days posttrauma. Late CC16 neutralization did not provide any survival benefits. On the whole, the present study demonstrated that neutralizing CC16 confirmed its antiinflammatory potential in this doublehit ALI model. Early CC16 neutralization prolonged survival within 60 h; however, no survival benefits were observed after 6 days postCLP in any group.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Traumatismos Torácicos
/
Uteroglobina
/
Sepsis
/
Lesión Pulmonar Aguda
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania