title: Fracture initiates systemic inflammatory response syndrome through recruiting polymorphonuclear leucocytes.
abstract: Fracture, a common type injury in trauma patients, often results in the development of the systemic inflammatory response syndrome (SIRS). Though the mechanism of the fracture-initiated SIRS still remains not well characterized, it is well documented that the polymorphonuclear leucocytes (PMN) play an important role in the inflammatory process. We hypothesize that fractures recruit PMN to the local tissue, which is followed by an increase in the number of peripheral PMN and initiation of SIRS. In the current study, we established a closed femoral fracture rat model. We evaluated the levels of MPO, IL-1β and CINC-1 in fractured tissue homogenate, and we measured the levels of IL-6 and IL-10, the biomarkers for systemic inflammatory response, in the rat sera. In clinical part of the study, we collected blood from patients with isolated closed femoral fractures and evaluated PMN-related chemoattractants (IL-8, IL-1β and G-CSF) and the number of peripheral PMN. We further evaluated the level of mitochondrial DNA in the local haematoma of fracture and the circulating plasma of the patients with fracture. In the animal model of closed femoral fracture, we found a significant recruitment of PMN to the local tissue after fracture, which correlates with the elevated MPO level. We also showed that the concentration of IL-1β and CINC-1 in local tissue is significantly increased and might be responsible for the PMN recruitment. Recruitment of PMN to the local tissue was accompanied with a significant increase in the systemic levels of IL-6 and IL-10 in serum. In the patients with closed femoral fracture, we observed an increase in the number of peripheral PMN and PMN-related chemoattractants, including IL-8, IL-1β and G-CSF. The level of mitochondrial DNA in the local haematoma of fracture and the circulating plasma of patients were significantly higher compared to the healthy volunteers. Our data suggest that fracture released mitochondrial DNA into the local haematoma of fracture, which recruited the PMN into the local tissue via chemokines (IL-1β and CINC-1), then increased the numbers of peripheral PMN and SIRS related cytokines in serum (IL-6 and IL-10). This might be the mechanism of the fracture-initiated SIRS.
authors.affiliation: Department of Orthopaedic Surgery, Beijing Army General Hospital, Nanmencang No. 5, Dongcheng District, Beijing, 100700, China.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Beijing Army General Hospital, Nanmencang No. 5, Dongcheng District, Beijing, 100700, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, Beijing Army General Hospital, Nanmencang No. 5, Dongcheng District, Beijing, 100700, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Orthopaedic Surgery, Beijing Army General Hospital, Nanmencang No. 5, Dongcheng District, Beijing, 100700, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Orthopaedic Surgery, Beijing Army General Hospital, Nanmencang No. 5, Dongcheng District, Beijing, 100700, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Orthopaedic Surgery, Beijing Army General Hospital, Nanmencang No. 5, Dongcheng District, Beijing, 100700, China. suntiansheng-@163.com.
authors.forename: Tiansheng
authors.initials: T
authors.lastname: Sun
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis; D004272:DNA, Mitochondrial / Q000378:metabolism; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology*
chemical_list: D054360:Chemokine CXCL1; D018925:Chemokines; C513297:Cxcl1 protein, rat; D004272:DNA, Mitochondrial; D018836:Inflammation Mediators; D016179:Granulocyte Colony-Stimulating Factor
keywords: Chemokine; Fracture; PMN; Systemic inflammatory response syndrome