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Association Between NLRP3 Signaling Pathway Activation And Complications In Patients With Multiple Trauma

Posted on:2019-11-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:M J ZhouFull Text:PDF
GTID:1364330545451255Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective: Multiple trauma is life-threatening with high disability and mortality,often accompanied by systemic inflammatory response syndrome(SIRS),sepsis,multiple organ dysfunction syndrome(MODS).It is,thus,of great importance for medical practitioners to assess the severity and diagnose the complications in order to treat the patients early.The present study was to study the activation state of inflammatory factors as NLRP3,IL-1β and IL-18 in patients with multiple trauma in the course of injury,and to clarify the correlation between the severity of trauma and the expression of these inflammatory factors,and the significance of the occurrence of traumatic subsequent changes.Methods: 100 patients with multiple trauma who visited the emergency trauma center of Shanghai Sixth People’s Hospital during August 2015 and July 2016 were enrolled prospectively,and meanwhile 40 healthy volunteers were enrolled as the control group.The severity of multiple trauma was scored according to the severity of trauma(Injury severity score,ISS).Sepsis is defined as a diagnostic standard according to The International Guidelines for the Treatment of Severe Sepsis and Septic Shock 2012.These patients were divided into 2 groups according to ISS at the time of admission: mild trauma group and severe trauma group.Serum procalcitonin was detected by electrochemiluminescence immunoassay.Lymphocyte subsets were analyzed by flow cytometry.IgG,IgA and IgM were detected by rate scattering turbidimetry.The concentrations of IL-1β and IL-18 in peripheral blood were measured by enzyme linked immunosorbent assay.The contents of NLRP3 and Caspase-1 in peripheral blood mononuclear cells(PBMC)were detected by Western blot.Results: 1)Of all the trauma patients,56% were complicated with MODS,39% were with SIRS,40% were with sepsis,and 10% died.The median hospital stay was 15 days.Severe trauma patients had higher peripheral blood neutrophils ratio,longer hospitalization days,higher MODS incidence(P < 0.01),and higher fatality rate(P < 0.05)when compared with mild group.The proportion of neutrophilic granulocyte,hospitalization days,mortalities,and incidences of MODS were positively correlated with the severity of the trauma(P < 0.05).2)The serum levels of IL-1β and IL-18 were significantly increased in both mild and severe groups compared with the normal group during different time periods after trauma(P < 0.01).Among the patients,IL-1β and IL-18 levels were higher in severe group than in mild group(P < 0.05).There was a correlation between IL-1β and IL-18 levels and trauma severity.A logistic regression analysis showed that the peak levels of serum IL-1β and IL-18 were independent predictors of both SIRS(IL-1β: RR:1.12;95% CI: 1.05-1.18;P= 0.049;IL-18: RR:1.07;95% CI: 1.02-1.19;P = 0.039)and sepsis(IL-1β: RR:1.14;95% CI: 1.02-1.27;P=0.048;IL-18: RR:1.15;95% CI:1.09-1.35;P=0.028).Moreover,NLRP3 and Caspase-1 expressions in PBMC significantly increased in trauma patients than in normal subjects,suggesting an activation of NLRP3.3)The levels of CD4+ lymphocyte percentage and IgG/IgA/IgM were greatly decreased,and the levels of NK cell were increased in severe trauma patients than in mild ones(all P<0.05).4)Serum PCT levels in trauma patients peaked at 24 hours after trauma.The serum PCT level of 12 hours was an important predictor of sepsis,but not SIRS.Conclusions: 1)NLRP3-Caspase-1-IL-1β/IL-18 was active in patients with multiple trauma.The elevated levels of IL-1β/IL-18 had significant statistical correlation with the incidence of SIRS and sepsis.In addition,serum PCT level was also elevated in patients with multiple trauma.Its levels also had significant statistical correlation with the incidence of sepsis,but not SIRS.Our data suggested that the combination of serum IL-1β,IL-18 and PCT might be a predictive marker for the incident SIRS and sepsis.
Keywords/Search Tags:Multiple trauma, Interleukin-1β, Interleukin-18, Inflammasome, Sepsis
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