Study On The Level Of NLRP3 In The Cerebrospinal Fluid Of Patients With Bacterial Meningitis

BackgroundBacterial meningitis is an infectious disease of the central nervous system caused by various bacteria invading the meninges.It is estimated that in developed countries,the incidence of bacterial meningitis in adults is 0.8-2.6 per 100,000 every year,and the incidence in less developed countries may be 10 times higher.Despite effective antibiotic treatment,adjunctive dexamethasone treatment,intensive care and other related adjunctive treatments,the mortality and morbidity rates are still high.WHO reported that bacterial meningitis is still the leading cause of death worldwide,causing 3,400,000 deaths every year.About half of the survivors suffer from focal neurological dysfunction,including hearing loss,epilepsy,and cognitive impairment.The cost associated with meningitis is high,and it places a heavy burden on the family,society,and health care system.The pathogenesis of neuroinflammation in various neurological diseases has received more and more attention.Inflammasomes are important parts of the inflammatory response.The classic inflammasome is a intracellular protein complex consisting of pattern recognition receptor(PRR),the adaptor protein which is called apoptosis-associated speck-like protein containing a CARD(ASC),and pro-caspase-1 which activates the effector protein caspase-1 after the receptor recognizes various stimuli.Then caspase-1 activates pro-IL-1β and pro-IL-18,which produces IL-1β and IL-18 to mediate inflammation,or activates the GSDMD protein to mediate a special way of cell death,that is,apoptosis.It is a kind of inflammatory cell death,accompanied by cell lysis and death,releasing a large amount of pro-inflammatory factors.In fact,inflammasomes have been shown to be essential for the defense against infection by a variety of pathogens.However,few studies have focused on the level of inflammasome-associated proteins in the cerebrospinal fluid of patients with bacterial meningitis.MethodFrom October 2018 to October 2020,a total of 40 patients with bacterial meningitis,20 patients with viral meningitis(viral meningitis)and 17 non-infectious disease cases were selected from patients who were hospitalized in the Department of Neurology or the subject biological sample bank of the First Affiliated Hospital of Zhengzhou University.They were recorded as BM group,VM group and Control group.All patients met the inclusion criteria of this study.This study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University.The ethical review numbers are 2018-KY-91 and 2019-KY-123.Before enrollment,the patients themselves or their authorized representatives signed the informed consent.All enrolled persons underwent lumbar puncture within 72 hours of admission and collected cerebrospinal fluid samples.The concentration of NLRP1,NLRP3,and NLRC4 in cerebrospinal fluid was determined by ELISA,At the same time,the intracranial pressure,the number of white blood cells,protein,sugar and chloride in the cerebrospinal fluid were measured,and the mRS score(modified Rankin scale scale)was used to to evaluate the severity of bacterial meningitis.SPSS 21.0 was used for statistical analysis,and Graphpadprism 9.0 was used to complete all the graphs.Result1.The concentration of NLRP3 in the cerebrospinal fluid of patients with bacterial meningitis was significantly higher than that of the VM group and the Control group,and the difference of NLRP3 in the cerebrospinal fluid of the VM group compared with the Control group was not statistically significant.There was no significant difference in the concentration of NLRP1 and NLRC4 among the three groups.2.There is no correlation between the concentration of NLRP3 in the cerebrospinal fluid of patients with bacterial meningitis and age,and there is no significant difference in the concentration of NLRP3 in the cerebrospinal fluid of patients with bacterial meningitis of different genders.3.Because of the differences in the expression of NLRP3,we further analyzed the correlation between NLRP3 and CSF-related indicators and mRS scores in the BM group,and found that there is no correlation between the NLRP3 concentration in the CSF and CSF related indicators,such as intracranial pressure,cerebrospinal fluid white blood cell count,protein,glucose and chloride levels.4.The mRS score of cerebrospinal fluid in patients with bacterial meningitis is positively correlated with the concentration of NLRP3 in cerebrospinal fluid.5.The area under curve(AUC)of cerebrospinal fluid NLRP3 for the diagnosis of bacterial meningitis is 0.876,and the maximum Youden index is 0.750.When the cut-off value of cerebrospinal fluid NLRP3 is 891.8pg/ml,the sensitivity and specificity for the diagnosis of bacterial meningitis were 85.0%and 80.0%,respectively.ConclusionNLRP3 inflammasome plays an important role in the pathogenesis of bacterial meningitis.Excessive inflammation may cause excessive neuronal damage and aggravate the severity of the disease.NLRP3 in cerebrospinal fluid is a potential indicator for the diagnosis of bacterial meningitis and the severity of the disease.