Study Of The Relationships Between Peripheral Immune Subpopulations And Post-stroke Infection Or Even Prognosis In Patients With Acute Spontaneous Intracerebral Hemorrhage

Part ? Relationship between peripheral neutrophil-tolymphocyte ratio and prognosis in patients with spontaneousintracerebral hemorrhageBackgroundSpontaneous intracerebral hemorrhage(s ICH)is one of the most devastating strokes in the world,especially in developing countries.Researches have confirmed that systemic immune inflammatory response plays an important role in secondary brain injury and affects the outcomes of stroke.However,the immune inflammatory response related to cytokines is not fully reflected in the ICH prognosis prediction model,because of the complexity of the cytokine network in vivo weakens the predictive value of single cytokine.The neutrophil-to-lymphocyte ratio(NLR)is relatively easy to obtain an accurate indicator of immune inflammation,which continuously reflects the status of innate and acquired immune inflammation in peripheral.A neutrophil is one of the innate immune cells that increased in the acute phase of stroke and secreted a large amount of nitric oxide synthase(i NOS)and matrix metal-9(MMP-9)with pro-inflammatory effects.This aseptic inflammatory cascade reaction aggravates cerebral edema and brain injury and affects the severity and prognosis of ICH.On the other hand,being reduced peripheral absolute lymphocyte count caused by stroke inducing systemic immunosuppression,can further curb the excessive inflammatory cascade and reduceinflammatory injury in the brain.However,excessive immunosuppression may increase the incidence of infection and be detrimental to clinical recovery.In acute coronary syndrome,ischemic stroke,diabetes,chronic obstructive pulmonary disease,tumor,sepsis,infectious disease,and liver failure and other diseases,NLR is predictive of its prognosis.s ICH exhibits a typical peripheral immune inflammatory imbalance.However,the predictive value of NLR is still controversial in its 3-month prognosis study.ObjectiveThe aim of the study was to evaluate the association of dynamic neutrophil-tolymphocyte ratio(NLR)with 3-month functional outcomes in patients with s ICH.MethodsWe identified 213 consecutive patients with s ICH hospitalized in The First Affiliated Hospital of Zhengzhou University from January 2017 to May 2018.Patients were divided into functional independence(FI)or unfavorable prognosis(UP)groups based on 3-month outcomes.Admission leukocyte counts within 24 hours of symptom onset were obtained,and the recorded fraction,where the numerator is neutrophil and the denominator is lymphocyte,as NLR0.Determined NLR1,NLR3,NLR7,and NLR14 were recorded on day 1(n = 77),day 3(n = 126),day 7(n = 123),and day 14(n = 105),respectively.Logistic regression analyses were used to identify the risk factors for unfavorable 3-month prognosis.ResultsThe patients' dynamic NLR was negatively associated with FI at 3-month followup.Furthermore,higher NLR or lower absolute lymphocyte count obtained at admission was independently risk factor for UP at 3 months(adjusted odds ratio [OR]: 1.06,95% confidence interval [CI]: 1.003,1.12;OR: 0.41,95% CI: 0.18,0.94,respectively).ConclusionHigher NLR and lower lymphocyte counts at early stages were predictive of 3-month unfavorable outcomes in s ICH patients.Part? Relationships between innate lymphocytes and post-ICH infection in spontaneous intracerebral hemorrhage patientsBackgroundICH accounts one of the severe types of stroke which is approximately 15-33% of total stroke.Its immune mechanism research found that except for the aseptic inflammatory response in local brain tissue,the contradictory state of stage reversible suppression of peripheral immune function also appeared in ICH.The inflammatory mechanism shows that infection can only occur when the innate immune defense fails,among them,peripheral lymphocytopenia is one of the risk factors of infection after ICH.Innate lymphoid cells(ILCs)are subsets lacking innate antigen receptors of lymphocyte.It mainly includes three subgroups,ILC1 expressing the transcription factor T-bet and secreting INF-? under the stimulation of IL-12 and IL-18.ILC2 expressing the transcription factors GATA3,ROR? and secreting IL-13 and IL-5 under the stimulation of TSLP,IL-33,and IL-25.And ILC3 expressing the transcription factor ROR?t and secreting IL-22,IL-17 a under the stimulation of IL-1 and IL-23.ILCs are derived from bone marrow primitive ILC and are widely distributed in the mucosal system including intestinal tract,skin,urethra,and lungs after blood transport.Human microflora includes symbiotic bacteria,fungi,and viruses,which are widely colonized in this mucosal system.ILCs play an important role in tissue remodeling,maintenance of mucosal integrity and promote the formation of lymphoid tissue,participate in the regulation of innate immune inflammatory response,and strengthen the immune response.Recently,ILCs have been extensively studied in the skin,intestinal tract and lung tissues.Part of the ILC2 and ILC3 was detected in the skin of psoriasis patients is thesource of peripheral blood migration.Patients with s ICH are prone to complicated respiratory and urinary tract infections in the acute phase,whose ILCs may be maladjusted and involved in the immune inflammatory mechanism of ICH infection.ObjectiveTo describe ILCs and cytokines including IL-1?,IL-6,and TNF-? in patients with s ICH;and to analyze the relationships between these inflammatory factors and postICH infection.MethodsA number of 80 patients with s ICH met the inclusion criteria and finished the blood routine examination on day1 after onset.Among these,71 patients were retested blood on day7,and 59 patients were retested blood on day14.40 healthy subjects with age and sex matching were selected as the control group.Flow cytometry was used to detect ILCs,and IL-1?,IL-6,TNF-? concentrations were tested by ELISA.Quantitatively analyzing white blood cell(WBC)includes absolute neutrophil count(ANC),absolute lymphocyte count(ALC),B lymphocyte,ILCs,and cytokines concentrations.The method of Spearman's or Kendall's correlation was used to analyze the relationship between ILCs count and post-ICH infection.Results1.Compared to control subjects,WBC(mainly ANC)was significantly increased,ALC was decreased in s ICH patients at day1,day7,and day14.ILCs especially ILC2 and ILC3 decreased significantly at day 1 and day 7.2.The concentrations of IL-1?,IL-6 and TNF-? at day1,day7 and day14 were synchronously increased in s ICH patients;and elevated IL-1(r = 0.244,p = 0.029*),IL-6(r = 0.280,p = 0.012*),TNF-?(r = 0.374,p ? 0.001***)were positively correlated to higher ANC at day1.3.ALC and ILCs were negatively correlated to post-ICH infection,while B lymphocyte count hasn't been proved relating to post-ICH infection.ConclusionPatients with s ICH maintained an active inflammatory response in the acute phase,with the decreased ALC,ILC2 and ILC3;in addition,decreased ALC and ILCs were associated with post-ICH infection.