Investigation On The Role And Potential Mechanism Of Chemokine CXCL16 In Septic Inflammatory Response

Objective: Sepsis is an infection that causes dysregulation of the host’s immune response and leads to life-threatening organ dysfunction.CXCL16 plays a role in a variety of inflammatory diseases,but the role of CXCL16 in the immune response process of sepsis is still unknown.Therefore,the purpose of this study is to explore the expression of the chemokine CXCL16 in sepsis,its role in the prognosis monitoring of sepsis,and the immune inflammatory response process.Methods: Collected from Chongqing medical university second affiliated hospital intensive care unit(ICU)in serum of 55 patients with sepsis,the first affiliated hospital of Chongqing medical university normal physical examination of serum levels of 30 patients,by enzyme-linked immunosorbent assay(Elisa)detection in patients and normal serum concentrations of CXCL16 chemotactic factor,and clinical data,using the receiver-operating characteristic curve(ROC)and correlation analysis to know CXCL16 in sepsis in the value of clinical diagnosis and prognosis prediction.C57BL/6 mice were treated with cecal ligation and puncture(CLP)to establish sepsis model.The mice were intraperitoneally injected with CXCL16 recombinant protein.The role of CXCL16 in the inflammatory reaction process of mice sepsis was analyzed by detecting the concentration of CXCL16 in mice,observing the survival days and status of mice,and staining of pathological sections of tissue specimens.Different types of inflammatory cytokines were analyzed,and the phagocytosis ability of inflammatory cells was detected to further illustrate the potential mechanism of CXCL16 in the inflammatory response process of sepsis.Meanwhile,mice with sepsis were treated with anti-CXCL16 antibody protein to observe its therapeutic effect.Results: Compared with the healthy physical examination,CXCL16 in sepsis patient’s serum level significantly increases,the area under the ROC curve shows that CXCL16 28 days in the predicting mortality of patients with sepsis has potential value,the correlation analysis showed that concentrations of CXCL16 and sepsis patients with Chinese super sensitive c-reactive protein(CRP),calcitonin(PCT)and white blood cell count(WBC)and SOFA scores were positively correlated.In CLP build of sepsis in C57 BL / 6 mice model,CXCL16 in serum,peritoneal lavage(PLF)and proteins in tissues were significantly increases,CXCL16 in mice significantly increased mortality in mice after treated by recombinant protein,liver,lung,and kidney tissue damage is aggravating,liver function index of serum ALT,AST and renal index of serum Urea and Creatinine increases,biopsy pathologic score increased significantly,prompt CXCL16 has the role of immune injury;The number of neutrophils and macrophages and the release of inflammatory factors were increased,and the concentrations of IL-6,IL-8,TNF-α and IFN-γ were increased,suggesting that CXCL16 could promote the inflammatory response during the immune process in sepsis.After anti-CXCL16 treatment,the mortality rate and organ tissue injury of mice were reduced,and the serum indexes of liver and kidney function were decreased.The antibody treatment had certain effect.Conclusions: The elevated concentration of CXCL16 in patients with sepsis is correlated with the severity and mortality of sepsis to some extent.CXCL16 can promote the inflammatory response in the immune process of sepsis,increase the damage of relevant organs and tissues,aggravate the recruitment of inflammatory cells and the release of inflammatory factors,and accelerate the death of sepsis mice.In addition,anti-CXCL16 protein can prolong the survival time of mice,and the inflammatory response is reduced by the reduction of organ tissue injury and the secretion of inflammatory factors.