脓毒症患者危重程度与血清IL-6的相关性分析

1、脓毒症患者危重程度与血清IL-6的相关性分析刘占国，谭晓莹，周 健，唐 颖，蔡 靓，杨祥锐，常 平 （510282 广州，南方医科大学珠江医院重症医学科）摘要 目的 探讨脓毒症患者血清白细胞介素-6（IL-6）水平与疾病危重程度的关系。方法 选取29名脓毒症患者为研究对象，在进入ICU 24 h小时内对其进行APACHE和SOFA评分，同时留取血清标本。根据IL-6浓度将患者分为3组：IL-6 low低浓度组（50 ng/L）、IL-6 mid中浓度组（50100 ng/L）和IL-6 hig高浓度组（100350 ng/L），分析血清IL-6水平与患者APACHE评分及SOFA评分的相关性。

2、结果 IL-6低中高3个浓度组的APACHE评分分别为15.224.09、16.756.86和22.585.45，3组差异有显著性（P=0.012）；3组SOFA评分分别为8.891.76、8.752.60和12.832.51，3组差异有显著性（P=0.000）。相关性分析显示IL-6水平与APACHE和SOFA评分均呈线性显著正相关（r=0.50，P=0.006；r=0.62，P=0.000)。结论 脓毒症患者血清IL-6浓度与疾病的危重程度具有显著的正相关性，可以作为反映病情变化的标志物。关键词 脓毒症；白细胞介素-6；APACHE评分；SOFA评分中图法分类号 文献标志码 ACorrel

3、ation analysis between the level of serum IL-6 and severity of septic patientsLiu Zhanguo, Tan Xiaoying, Zhou Jian, Tang Ying, Cai Jing, Yang Xiangrui, Chang Ping（Department of ICU, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China）Abstract Objective To explore the relationshi

4、p between the level of serum interleukin-6(IL-6) and severity of patients with sepsis. Methods 29 septic patients were selected for the analysis of correlation between serum IL-6 level and APACHE scores and SOFA scores respectively within 24 hours after admission to ICU. The patients were divided in

5、to three groups, which are IL-6 low（50ng/L）, IL-6 middle（50-100 ng/L）and IL-6 high（100-350 ng/L）group, according to IL-6 level. Result APACHE scores were 15.224.09 in the septic patients in serum IL-6 low group, 16.756.86 in IL-6 mid group, 22.585.45 in IL-6 high group. SOFA scores were 8.891.76 in

6、the septic patients in serum IL-6 low group, 8.752.60 in IL-6 mid group, 12.832.51 in IL-6 high group. Serum IL-6 levels were positively correlated with the APCHE scores and SOFA scores significantly（r=0.50，P=0.006，r=0.62，P=0.000). Conclusion Serum IL-6 levels are positively correlated with the seve

7、rity of septic patients significantly and could be used as a biomarker to evaluate the critical degree.Key words sepsis; interleukin-6(IL-6); APACHE; SOFASupported by NSFC (81101451)，Natural Science Foundation of Guangdong Province（S2011010003106）and Medical Reserch Funds of Guangdong Province(B2011

8、208).Corresponding author: Chang Ping, E-mail: 基金项目 自然科学基金(81101451)；省自然基金（S2011010003106）；东省医学科学技术研究基金（B2011208）通信作者 常 平， E-mail: 脓毒症(sepsis)是危重患者主要的死因之一，发病及致死机制复杂，病情进展迅速，死亡率高 ADDIN EN.CITE Adib-Conquy2012373717Adib-Conquy, M.Cavaillon, J. M.Unite cytokines et inflammation, departement infection et

9、 epidemiologie, Institut Pasteur, 28, rue du Dr-Roux, 75015 Paris, France.Host inflammatory and anti-inflammatory response during sepsis.Pathol Biol (Paris)Pathol Biol (Paris)2012/05/012012Apr 27Reponse inflammatoire et anti-inflammatoire de l'hote au cours du sepsis.1768-3114 (Electronic)0369-

10、8114 (Linking)22542429/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22542429S0369-8114(12)00047-8 pii10.1016/j.patbio.2012.03.011FreFry2012414117Fry, D. E.Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. dfrySepsis, systemic infl

11、ammatory response, and multiple organ dysfunction: the mystery continuesAm SurgAm Surg1-87812012/01/26Adrenal Cortex Hormones/therapeutic useAntibodies, Monoclonal/therapeutic useClinical Trials as TopicHumansMultiple Organ Failure/*drug therapy/*physiopathologyProtein C Inhibitor/therapeutic useSep

12、sis/*drug therapy/*physiopathologySystemic Inflammatory Response Syndrome/*drug therapy/*physiopathologyTumor Necrosis Factor-alpha/antagonists & inhibitors2012Jan1555-9823 (Electronic)0003-1348 (Linking)22273282/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22273282engHotchkiss20

13、063317Hotchkiss, R. S.Nicholson, D. W.Department of Anesthesiology, Washington University School of Medicine, Campus Box 8054, 660 South Euclid, St Louis, Missouri 63110, USA.Apoptosis and caspases regulate death and inflammation in sepsisNat Rev ImmunolNat Rev Immunol813-226112006/10/14Animals*Apop

14、tosis/immunologyCaspases/antagonists & inhibitors/*metabolismCell CommunicationHumansInflammation/enzymology/immunology/pathology/therapyProtease Inhibitors/therapeutic useSepsis/*enzymology/immunology/*pathology/therapy2006Nov1474-1733 (Print)1474-1733 (Linking)17039247/entrez/query.fcgi?cmd=Retrie

15、ve&db=PubMed&dopt=Citation&list_uids=17039247nri1943 pii10.1038/nri1943engXu20095517Xu, J.Zhang, X.Pelayo, R.Monestier, M.Ammollo, C. T.Semeraro, F.Taylor, F. B.Esmon, N. L.Lupu, F.Esmon, C. T.Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.Extracellular histones are major mediators of

16、death in sepsisNat MedNat Med1318-2115112009/10/27AnimalsAntibodies/pharmacology/therapeutic useCattleCell Line, TransformedDisease Models, AnimalEndothelium/drug effects/pathology/ultrastructureEscherichia coli/physiologyExtracellular Fluid/drug effects/*metabolismFlow CytometryHemorrhage/etiology/

17、pathologyHistones/drug effects/immunology/*metabolism/pharmacologyKidney Diseases/metabolismMacrophages/drug effects/metabolism/ultrastructureMiceMicroscopy, Electron, Transmission/methodsNeutrophils/drug effects/pathologyOligopeptides/pharmacology/therapeutic usePapioPolysaccharides/adverse effects

18、Sepsis/drug therapy/etiology/*mortality/*pathologyTumor Necrosis Factor-alpha/adverse effects2009Nov1546-170X (Electronic)1078-8956 (Linking)19855397/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19855397nm.2053 pii10.1038/nm.2053eng1-4。炎症介质在导致多器官损伤的过程中发挥了重要作用，IL-6是典型的炎症介质，是导致脓毒症患

19、者组织是什么？损伤的重要因素之一。研究显示IL-6可能是一个潜在的标志物用于反映脓毒症的危重程度一个潜在的标志物 ADDIN EN.CITE Bozza20072217Fernando A Bozza Jorge I SalluhAndr M JapiassuMarcio Soares Edson F AssisRachel N Gomes Marcelo T Bozza Hugo C Castro-Faria-NetoPatrcia T BozzaCytokine profiles as markers of disease severity in sepsis: a multiplex a

20、nalysisCritical CareCritical Care1-81122007Damas19921117Damas, P.Ledoux, D.Nys, M.Vrindts, Y.De Groote, D.Franchimont, P.Lamy, M.Department of Anesthesiology, University of Liege, Belgium.Cytokine serum level during severe sepsis in human IL-6 as a marker of severityAnn SurgAnn Surg356-6221541992/04

21、/01AdultAgedAged, 80 and overBacteremia/*bloodC-Reactive Protein/analysisCause of Death*Critical IllnessFemaleHumansInterleukin-1/*analysisInterleukin-6/*analysisMaleMiddle AgedSeverity of Illness IndexShock/bloodShock, Septic/*bloodSurvival RateTumor Necrosis Factor-alpha/*analysis1992Apr0003-4932

22、(Print)0003-4932 (Linking)1558416/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1558416engChawla2007111117Chawla, L. S.Seneff, M. G.Nelson, D. R.Williams, M.Levy, H.Kimmel, P. L.Macias, W. L.Department of Anesthesiology and Critical Care Medicine, The George Washington University

23、Medical Center, Washington, DC 20037, USA. lchawlaElevated plasma concentrations of IL-6 and elevated APACHE II score predict acute kidney injury in patients with severe sepsisClin J Am Soc NephrolClin J Am Soc Nephrol22-30212007/08/21*ApacheAcute Kidney Injury/blood/*epidemiology/immunologyAgedBiol

24、ogical Markers/bloodFemaleHumansInterleukin-6/*bloodMaleMiddle AgedMultivariate AnalysisPredictive Value of TestsProportional Hazards ModelsProspective StudiesProtein C/*therapeutic useRecombinant Proteins/therapeutic useRisk FactorsSepsis/*drug therapy/*epidemiology/immunologySeverity of Illness In

25、dex2007Jan1555-905X (Electronic)1555-9041 (Linking)17699383/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17699383CJN.02510706 pii10.2215/CJN.02510706engAdib-Conquy373717Adib-Conquy, M.Cavaillon, J. M.Unite cytokines et inflammation, departement infection et epidemiologie, Institu

26、t Pasteur, 28, rue du Dr-Roux, 75015 Paris, France.Host inflammatory and anti-inflammatory response during sepsis.Pathol Biol (Paris)Pathol Biol (Paris)2012/05/012012Apr 27Reponse inflammatoire et anti-inflammatoire de l'hote au cours du sepsis.1768-3114 (Electronic)0369-8114 (Linking)22542429/

27、entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22542429S0369-8114(12)00047-8 pii10.1016/j.patbio.2012.03.011FreFugger1993525217Fugger, R.Zadrobilek, E.Gotzinger, P.Klimann, S.Rogy, M.Winkler, S.Andel, H.Mittelbock, M.Roth, E.Schulz, F.et al.,First Surgical Department and Intensive

28、Care, University of Vienna, School of Medicine, Austria.Perioperative TNF alpha and IL-6 concentrations correlate with septic state, organ function, and APACHE II scores in intra-abdominal infectionEur J SurgEur J Surg525-9159101993/10/01Abdomen/*surgeryAdolescentAdultAgedFemaleGram-Negative Bacteri

29、al Infections/*immunology/*surgeryHumansInterleukin-6/*bloodLactates/bloodMaleMiddle AgedProspective StudiesSeverity of Illness IndexShock, Septic/*immunology/*surgerySyndromeTumor Necrosis Factor-alpha/*analysis1993Oct1102-4151 (Print)1102-4151 (Linking)8286509/entrez/query.fcgi?cmd=Retrieve&db=Pub

30、Med&dopt=Citation&list_uids=8286509engRemick20056617Remick, D. G.Bolgos, G.Copeland, S.Siddiqui, J.Department of Pathology, University of Michigan, Ann Arbor, MI 48109-0602, USA. remickdRole of interleukin-6 in mortality from and physiologic response to sepsisInfect ImmunInfect Immun2751-77352005/04

31、/23AnimalsBody TemperatureCecum/injuriesDisease Models, AnimalHumansInterleukin-6/*blood/deficiency/geneticsLigationMiceMice, Inbred C57BLMice, KnockoutMotor ActivityOrgan SpecificityPuncturesSepsis/immunology/*mortality/pathology/*physiopathologySeverity of Illness IndexWomen2005May0019-9567 (Print

32、)0019-9567 (Linking)15845478/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1584547873/5/2751 pii10.1128/IAI.73.5.2751-2757.2005engCarbonell2004595917Carbonell, N.Blasco, M.Ferreres, J.Blanquer, J.Garcia-Ramon, R.Mesejo, A.Miguel, A.Intensive Care Unit, Hospital Clinico Universitar

33、io, Valencia, Spain. edurnecarbonellyahoo.esSepsis and SOFA score: related outcome for critically ill renal patientsClin NephrolClin Nephrol185-926232004/10/16Acute Kidney Injury/*physiopathologyAdultAgedAged, 80 and overCardiovascular Diseases/physiopathologyCreatinine/bloodCritical IllnessFemaleHu

34、mansMaleMiddle AgedProspective StudiesSepsis/*physiopathology2004Sep0301-0430 (Print)0301-0430 (Linking)15481850/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15481850eng1, 5-10。本研究对29例脓毒症患者的IL-6水平和危重评分进行了相关性分析，旨在进一步明确IL-6和脓毒症危重程度的关系，评估IL-6是否可以作为反映脓毒症病情严重程度的指标。1 对象与方法1.1 研究对象 2011

35、年1月至2012年1月本院收治脓毒症患者29例，包括男性20例，女性9例，2676(55.4118.77)岁。其中原发病为肺炎17例，腹膜炎9例，胰腺炎3例，符合2001年美国危重病医学会欧洲危重病医学会美国胸科医师协会美国胸科协会美国外科感染学会（SCCMESICMACCPATSSIS）联席会议提出的脓毒症诊断标准 ADDIN EN.CITE Levy2003141417Levy, M. M.Fink, M. P.Marshall, J. C.Abraham, E.Angus, D.Cook, D.Cohen, J.Opal, S. M.Vincent, J. L.Ramsay, G.Rho

36、de Island Hospital, Brown University School of Medicine, 593 Eddy Street, Providence, RI 02903, USA.2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions ConferenceCrit Care MedCrit Care Med1250-63142003/04/12HumansMultiple Organ Failure/complications/diagnosisSepsis/complications/*diagnosis

37、Shock, Septic/diagnosisSystemic Inflammatory Response Syndrome/*diagnosis*Terminology as Topic2003Apr0090-3493 (Print)0090-3493 (Linking)12682500/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1268250010.1097/01.CCM.0000050454.01978.3Beng11。29例患者在进入ICU 24 h内对其进行APACHE和SOFA评分，并根据IL-

38、6水平分为高中低3组：IL-6低浓度组（50 ng/L）、IL-6中浓度组（50100 ng/L）和IL-6高浓度组（100350 ng/L）。临床资料详见表1。表1 脓毒症患者的临床资料组别IL-6低浓度组（n=9）IL-6中浓度组（n=8）IL-6高浓度组（n=12）年龄34-76岁26-65岁31-69岁女性3人2人4人男性6人6人8人腹膜炎1人2人6人胰腺炎0人0人3人肺炎8人6人3人IL-6浓度4-50ng/L50-100 ng/L100-350 ng/LAPACHEII评分9-2110-3016-34SOFA评分6-126-149-171.2 方法 于入院后24 h内进行脓毒症诊断

39、和APACHE、SOFA评分，同时留取血清样本(样本检测由珠江医院临床检验中心完成，正常值:IL-6：05.4 pg/ml)。采用SPSS 15.0统计软件，IL-6值低中高组间均数比较采用单因素方差分析One way ANOVA，血清IL-6水平和APACHE评分、IL-6和SOFA评分之间进行Pearson相关分析。2 结果 2.1 3组脓毒症患者情况IL-6低中高浓度3组IL-6浓度浓度单位是什么？分别为19.1713.24 ng/L、65.04 9.14 ng/L、186.0564.8 ng/L 0，3组之间均有显著性差异（P=0.000）。2.2 脓毒症患者的危重评分 IL-6低中高

40、3个浓度组的APACHEII评分分别为15.224.09、16.756.86和22.585.45，3组差异有显著性（P=0.012），IL-6高浓度组较IL-6低、中浓度组评分显著升高（P=0.005，P=0.029），IL-6中、低浓度组相比评分无显著性差异（P=0.573）。IL-6低中高3个浓度组的SOFA评分分别为8.891.76、8.752.60和12.832.51，3组差异有显著性（P=0.000），IL-6高浓度组较IL-6低、中浓度组评分显著升高（P=0.001， P=0.001），IL-6中、低浓度组相比评分无显著性差异（P=0.904）。2.3 脓毒症患者血清IL-6与AP

41、ACHE评分的相关性 血清IL-6与APACHE评分呈线性正相关（r=0.50，P=0.002006，图1)。 r=0.50P=0.006图1 脓毒症患者IL-6和APACHE评分的相关性分析2.4 脓毒症患者血清IL-6与SOFA评分的相关性 血清IL-6与SOFA评分呈线性正相关（r=0.62，P=0.000，图2)。r=0.5062P=0.006000图3 脓毒症患者IL-6和SOFA评分的相关性分析3 讨论脓毒症的发病及致死机制复杂，病情进展迅速，死亡率高，危重评分可以较为准确地反映疾病的危重程度、治疗效果及预后 ADDIN EN.CITE Adib-Conquy2012373717A

42、dib-Conquy, M.Cavaillon, J. M.Unite cytokines et inflammation, departement infection et epidemiologie, Institut Pasteur, 28, rue du Dr-Roux, 75015 Paris, France.Host inflammatory and anti-inflammatory response during sepsis.Pathol Biol (Paris)Pathol Biol (Paris)2012/05/012012Apr 27Reponse inflammato

43、ire et anti-inflammatoire de l'hote au cours du sepsis.1768-3114 (Electronic)0369-8114 (Linking)22542429/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22542429S0369-8114(12)00047-8 pii10.1016/j.patbio.2012.03.011FreFry2012414117Fry, D. E.Department of Surgery, Northwestern Un

44、iversity Feinberg School of Medicine, Chicago, Illinois, USA. dfrySepsis, systemic inflammatory response, and multiple organ dysfunction: the mystery continuesAm SurgAm Surg1-87812012/01/26Adrenal Cortex Hormones/therapeutic useAntibodies, Monoclonal/therapeutic useClinical Trials as TopicHumansMult

45、iple Organ Failure/*drug therapy/*physiopathologyProtein C Inhibitor/therapeutic useSepsis/*drug therapy/*physiopathologySystemic Inflammatory Response Syndrome/*drug therapy/*physiopathologyTumor Necrosis Factor-alpha/antagonists & inhibitors2012Jan1555-9823 (Electronic)0003-1348 (Linking)22273282/

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55、ogyKidney Diseases/metabolismMacrophages/drug effects/metabolism/ultrastructureMiceMicroscopy, Electron, Transmission/methodsNeutrophils/drug effects/pathologyOligopeptides/pharmacology/therapeutic usePapioPolysaccharides/adverse effectsSepsis/drug therapy/etiology/*mortality/*pathologyTumor Necrosi

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