头孢克洛独特的免疫学特性PPT课件

.,1,头孢克洛独特的免疫学特性,.,2,抗生素参与机体免疫反应,间接效应直接效应,.,3,间接效应,杀死细菌改变肠道菌群,抗原性防止细菌毒素效应,.,4,直接效应,激活宿主防御机制(多形核白细胞)激活巨噬细胞吞噬细胞伸出伪足包围细菌并吞入激活调理作用激活补体系统，使细菌易被吞噬并抑制细菌酶或毒素产生激活趋化作用使白细胞向细菌移动,.,5,影响生物学效应的抗菌药,对宿主防御系统无活性（一般的内酰胺类抗生素）抑制免疫功能（四环素类）与免疫系统协同作用（大环内酯类、喹诺酮类）增强免疫功能（某些头孢烯内酰胺类）,.,6,影响体外免疫反应的抗菌药,.,7,增强吞噬细胞功能的内酰胺类,.,8,文献报道,希刻劳当体外试验敏感，临床和细菌学的疗效为95%当体外药敏耐药，临床疗效为84%。,.,9,LeuenbergerP,VrantchevS,Cefactorversusamoxicillininthetreatmentofbacterialpneumonia:acomparativedouble-blindstudy.EurJClinMicrobiology.1983;2(11):11-6.ZeluffB,CatchpoleM,LoweP,etal.Cefadroxilcomparedwithcefaclorinthetreatmentofstreptococcalpneumoniainadults.Drugs.1986;32Suppl;3:39-42.SchleupnerCJ,AnthonyWC,TanJ,etal.Blindedcomparisonofcefuroximetocefaclorforlowerrespiratorytractinfections.ArchinternMed.1988;148(2):343-42.OberlinJA.HyslopDL,Cefaclortreatmentofupperand;owerrespiratorytractinfectionscausedbymoraxellacatarrhalis.PediatrinfectDISJ,1990;9(1):41-4.WettengelR,VetterN,WaardenburgFA.Clarithromycirversuscefaclorforthetreatmentofmild-to-moderateacutebacterialbronchitis.JAntimicrobChemother.1993;31:963-72.ODohertyB.Anopencomparativestudyofazithromycinversuscefaclorinthetreatmentofpatientswithupperrespiratorytractinfections.JAntimicrobChemother1996;37(SupplC):71-81.TurikMA,JohnsDJr,Comparisonofcefaclorandcefuroximeaxetilinthetreatmentofacuteotitismediawitheffusioninchildrenwhofailedamoxicillintherapy.JChemother,1998;10(4):306-12.HaczynskiJ,BardadinJ,GryczynskaD,etal.Acomparativestudyofcefaclorvs.amoxicillin/clavulanateintonsillopharyngitis.MedSciMonitor.2001;7(5):1016-22.EspositoS,MarchisioP,BososS,etal.Comparativeefficacyandsafetyof5-daycefaclorand10-dayamoxicillinteeatmentofgroupAstreptococcalpharyngitisinchildren.IntJAntimicrobialAgents.2002;20(1)28-33.HaczynskiJ,ChmielikM,BienSetal.Acomparativestudyofcefaclorvs.Amoxicillin/clavulanateinpediatricpharyngotonsillitis.MedSciMonit.2003;9(3):P129-35.CataniaS,GalloA.Clinicalefficacyandtolerabilityofshortcoursetherapywithcefaclorcomparedwithlong-termtherapyfortreatmentofacuteotitismediainchildren.InfezMed.2004;12(4):259-65.AggarwalM,SinhaR,MuraliMV,etal.Comparativeefficacyandsafetyevaluationofcefaclorvsamoxycillin+clavulanateinchildrenwithAcuteOtitisMedia(AOM).IndianJPediatr.2005;72(3):233-8.,希刻劳治疗社区呼吸道感染临床疗效值得信赖,94,97,98,97,96,98,98,90,94,临床有效率,.,10,为什么体外药敏部分细菌对希刻劳不敏感，但治疗后的临床疗效却很好？,.,11,头孢克洛的免疫调节作用,体外研究,.,12,希刻劳具有体内增效抗菌特性,Ref:JChemother,1998;10(2):91-96.,在人体内,希刻劳与中性白细胞的相互作用,使希刻劳抗菌活性显著加强（对于肺炎链球菌的MBC仅为原来1/8）,加入中性粒细胞前,加入中性粒细胞后,MBC降低到1/8,.,13,头孢克洛对金葡菌体内外疗效比较(第一组),希刻劳具有体内增效抗菌特性,.,14,头孢克罗对金葡菌体内及体外疗效比较(第二组),希刻劳具有体内增效抗菌特性,.,15,希刻劳体内疗效明显大于体外药敏试验,实验表明：希刻劳对革兰氏阳性菌体外的MBC要明显大于体内,头孢克洛可增强吞噬细胞的趋化及氧化作用。头孢克洛可抑制白细胞合成丙三烯，抑制氧自由基形成和组胺释放。,艾效曼,赵莹,张秀珍.头孢克洛免疫调节功能体外实验,.,16,头孢克洛对流感嗜血杆菌体内和体外模拟试验,希刻劳具有体内增效抗菌特性,.,17,头孢克洛对卡他莫拉菌菌体内和体外模拟试验,希刻劳具有体内增效抗菌特性,.,18,实验表明：希刻劳对革兰氏阴性菌体外的MBC要明显大于体内,头孢克洛可增强吞噬细胞的趋化及氧化作用。头孢克洛可抑制白细胞合成丙三烯，抑制氧自由基形成和组胺释放。,艾效曼，胡云建，张秀珍修改.头孢克洛对流感嗜血杆菌和卡他莫拉菌体内模拟实验,希刻劳体内疗效明显大于体外药敏试验,.,19,头孢克洛体内模拟试验MBC值比较ug/ml,希刻劳体内疗效明显大于体外药敏试验,.,20,头孢克洛对细胞因子的免疫调节作用,体内研究,.,21,感染引起的全身炎症反应及随后机体的代偿性抗炎症反应是导致脏器功能损伤的主要原因,SergioZanotti,SseemKumar,AnandKumar,Cytokinemodulationinsepsisandsepticshock.ExpertOpinInvestig.Drugs2002,11(8):1061-1075,.,22,细菌感染治疗结果的决定因素,药物的抗菌作用,宿主的免疫功能,+,通过体外药敏试验来判断,通过免疫功能测定先天免疫获得性免疫,ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647,.,23,有些抗菌药具有免疫调节作用,抗生素对宿主先天免疫和获得性免疫的作用可能影响治疗结果头孢地嗪免疫调节作用最大头孢噻肟有免疫抑制作用头孢克洛也具有免疫调节作用体外增强粒细胞的吞噬作用和杀菌活性体外增强巨噬细胞的吞噬作用和杀菌活性体外增强多形核中性粒细胞(PMN)的活性可能对免疫细胞因子也有调节作用,.,24,免疫指数定义,.,25,头孢克洛的免疫调节作用可影响机体免疫防御机制,希刻劳被证实有提高机体免疫反应的作用,抗生素能提高机体的细胞免疫和体液免疫。抗生素能降低细菌的毒力因子或使其更易被免疫攻击。抗生素能帮助机体免疫功能的恢复。,1、JM.T.HAMILTON-MILLERDepartmentofMedicalMicrobiology,RoyalFreeandUniversityCollegeMedicalSchool.London,U.K.ImmunopharmacologyofAntibiotics:DirectandIndirectImmunomodulationofDefenceMechanismsLEADINGARTICLEJournalofchemotherapyVol2001;13(2):107-111,.,26,头孢克洛对免疫的调节作用,动物试验,ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647,.,27,细胞因子与免疫功能,I型细胞因子：促炎症细胞因子IFN-、TNF-、IL-1、IL-2、IL-12、IL-18刺激细胞介导的免疫效应细胞，如巨噬细胞、细胞毒性T细胞以及NK细胞上调迟发型超敏反应调节免疫，参与清除胞内病原体2型细胞因子IL-4、IL-5、IL-6、IL-10、IL-13主要调节体液免疫应答，刺激IgG1和IgE的生成下调巨噬细胞、细胞毒性T细胞以及NK细胞的功能活性3型细胞因子TGF-主要调节体液免疫应答，刺激IgG1和IgE的生成下调巨噬细胞、细胞毒性T细胞以及NK细胞的功能活性,.,28,实验方法,大鼠口服头孢克洛剂量是10、50或100mg/kg/d疗程3天或6天对照组口服磷酸盐缓冲液(PBS)吸入CO2处死动物取动物脾脏，制备细胞悬液进行免疫试验淋巴细胞增殖试验测定各种细胞因子水平,ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647,.,29,主要结果,.,30,头孢克洛刺激淋巴细胞增殖,ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647,细胞增殖指数,P=0.001,P=0.001,P=0.002,P=0.045,*P值是与头孢克洛组与赋形剂组相比t检验的结果,P=0.002,.,31,头孢克洛刺激淋巴细胞增殖,ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647,细胞增殖指数,P0.001,P0.001,P0.001,P=0.001,P=0.001,P=0.004,*P值是与头孢克洛组与赋形剂组相比t检验的结果,.,32,头孢克洛刺激TNF-的合成,ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647,pg/ml,.,33,头孢克洛刺激TNF-的合成,ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647,pg/ml,.,34,头孢克洛刺激IFN-的合成,ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647,pg/ml,*P0.001，头孢克洛组与赋形剂组相比t检验的结果,*,*,.,35,头孢克洛刺激IFN-的合成,ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647,pg/ml,*P0.001，头孢克洛组与赋形剂组相比t检验的结果,*,.,36,头孢克洛刺激IL-2的合成,ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647,pg/ml,*P=0.001，头孢克洛组与赋形剂组相比t检验的结果,*,.,37,头孢克洛刺激IL-2的合成,ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647,pg/ml,*P0.001，*p=0.007，头孢克洛组与赋形剂组相比t检验的结果,*,*,*,.,38,头孢克洛降低IL-4水平,ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647,pg/ml,*P0.001，*p=0.003，头孢克洛组与赋形剂组相比t检验的结果,*,*,*,.,39,头孢克洛降低IL-4水平,ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647,pg/ml,*P0.001，*p=0.001，头孢克洛组与赋形剂组相比t检验的结果,*,*,*,.,40,头孢克洛降低IL-6水平,ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647,pg/ml,.,41,头孢克洛降低IL-6水平,ManganoK,etal.Immunomodulatorypropertiesofcefaclor:invivoeffectoncytokinereleaseandlymphoproliferativeresponseinrats.JournalofChemotherapy2006,18(6):641-647,pg/ml,*P0.001，*p=0.008，*p=0.014，头孢克洛组与赋形剂组相比t检验的结果,*,*,*,.,42,头孢克洛刺激IL-10的合成,ManganoK,etal.Immunomodulatoryprop