Contributing factors in the development of acute lung injury in a murine double hit model.

Abstract

Blunt chest (thoracic) trauma (TxT) is known to contribute to the development of secondary pulmonary complications. Of these, acute lung injury (ALI) is common especially in multiply injured patients and might not only be due to the direct trauma itself, but seems to be caused by ongoing and multifactorial inflammatory changes. Nevertheless, the exact mechanisms and contributing factors of the development of ALI following blunt chest trauma are still elusive. 60 CL57BL/6N mice sustained either blunt chest trauma combined with laparotomy without further interventions or a double hit (DH) including TxT and cecal ligation puncture (CLP) after 24h to induce ALI. Animals were killed either 6 or 24h after the second procedure. Pulmonary expression of inflammatory mediators cxcl1, cxcl5, IL-1β and IL-6, neutrophil infiltration and lung tissue damage using the Lung Injury Score (LIS) were determined. Next to a moderate increase in other inflammatory mediators, a significant increase in CXCL1, neutrophil infiltration and lung injury was observed early after TxT, which returned to baseline levels after 24h. DH induced significantly increased gene expression of cxcl1, cxcl5, IL-1β and IL-6 after 6h, which was followed by the postponed significant increase in the protein expression after 24h compared to controls. Neutrophil infiltration was significantly enhanced 24h after DH compared to all other groups, and exerted a slight decline after 24h. LIS has shown a significant increase after both 6 and 24h compared to both control groups as well the late TxT group. Early observed lung injury with moderate inflammatory changes after blunt chest trauma recovered quickly, and therefore, may be caused by mechanical lung injury. In contrast, lung injury in the ALI group did not undergo recovery and is closely associated with significant changes of inflammatory mediators. This model may be used for further examinations of contributing factors and therapeutic strategies to prevent ALI.