头孢克洛独特的免疫学特性.ppt

1、a,1,头孢克洛独特的免疫学特性,a,2,抗生素参与机体免疫反应,间接效应 直接效应,a,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,a,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,a,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）,a,6,影响体外免疫反应的抗菌药,a,7,增强吞噬细胞功能的内

2、酰胺类,a,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%。,a,9,Leuenberger P,Vrantchev S,Cefactor versus amoxicillin in the treatment of bacterial pneumonia:a comparative double-blind study. Eur J Clin Microbiology.1983;2(11):11-6. Zeluff B, Catchpole M,Lowe P,et al. Cefadroxil compared with cefaclor i

3、n the treatment of streptococcal pneumonia in adults. Drugs. 1986;32 Suppl; 3:39-42. Schleupner CJ, Anthony WC, Tan J, et al. Blinded comparison of cefuroxime to cefaclor for lower respiratory tract infections. Arch intern Med. 1988; 148(2):343-42. Oberlin JA. Hyslop DL, Cefaclor treatment of upper

4、and; ower respiratory tract infections caused by moraxella catarrhalis. Pediatr infect DIS J, 1990;9(1):41-4. Wettengel R, Vetter N, Waardenburg FA. Clarithromycir versus cefaclor for the treatment of mild-to-moderate acute bacterial bronchitis. J Antimicrob Chemother. 1993;31:963-72. ODoherty B. An

5、 open comparative study of azithromycin versus cefaclor in the treatment of patients with upper respiratory tract infections. J Antimicrob Chemother 1996;37(Suppl C):71-81. Turik MA, Johns D Jr, Comparison of cefaclor and cefuroxime axetil in the treatment of acute otitis media with effusion in chil

6、dren who failed amoxicillin therapy. J Chemother, 1998;10(4):306-12. Haczynski J, Bardadin J,Gryczynska D, et al. A comparative study of cefaclor vs. amoxicillin/clavulanate in tonsillopharyngitis. Med Sci Monitor. 2001;7(5):1016-22. Esposito S,Marchisio P,Bosos S, et al. Comparative efficacy and sa

7、fety of 5-day cefaclor and 10-day amoxicillin teeatment of group A streptococcal pharyngitis in children. Int J Antimicrobial Agents. 2002;20(1)28-33. Haczynski J, Chmielik M, Bien S et al. A comparative study of cefaclor vs. Amoxicillin/ clavulanate in pediatric pharyngotonsillitis. Med Sci Monit.

8、2003;9(3):P129-35. Catania S, Gallo A. Clinical efficacy and tolerability of short course therapy with cefaclor compared with long-term therapy for treatment of acute otitis media in children. Infez Med. 2004;12(4):259-65. Aggarwal M, Sinha R, Murali MV, et al. Comparative efficacy and safety evalua

9、tion of cefaclor vs amoxycillin + clavulanate in children with Acute Otitis Media (AOM). Indian J Pediatr.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,a,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？,a,11,头孢克洛的免疫调节作用,体外研究,a,12,希刻劳具有体内增效抗菌特性,Ref:J Chemother,1998;10(2):91-96 .,在人体内,希刻

10、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,a,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,a,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,a,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,a,16,头孢克洛对流

11、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,a,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,a,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,a,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,a,20,头孢克洛对细胞因子的免疫调节作用,体内研究,a,21,感染引起的全身炎症反应

12、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,Sergio Zanotti,Sseem Kumar,Anand Kumar,Cytokine modulation in sepsis and septic shock.Expert Opin Investig.Drugs 2002,11(8):1061-1075,a,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,Mangano K, et al. Immunomodulatory properties of cefaclor: in vivo e

13、ffect on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 18(6):641-647,a,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,a,24,免疫指数定义,a,25,头孢克洛的免疫调节作用

14、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-MILLER Department of MedicalMicrobiology, Royal Free and University College Medical School. London, U.K. Immunopharmacology of Antibiotics:Direct and Indirect Immunomodulation of Defence M

15、echanisms LEADING ARTICLE Journal of chemotherapy Vol 2001;13(2):107-111,a,26,头孢克洛对免疫的调节作用,动物试验,Mangano K, et al. Immunomodulatory properties of cefaclor: in vivo effect on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 18(6):641-647,a,27,细胞因子与免疫功能,I型细胞因子：促炎

16、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,a,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

17、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,Mangano K, et al. Immunomodulatory properties of cefaclor: in vivo effect on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 18(6):641-647,a,29,主要结果,a,30,头孢克洛刺激淋巴细胞增殖,Mangano K, et al. Immunomodulator

18、y properties of cefaclor: in vivo effect on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 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,a,31,头孢克洛刺激淋巴细胞增殖,Mangano K, et al. Immunomodulatory properties of cefaclor: in vi

19、vo effect on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 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,a,32,头孢克洛刺激TNF-的合成,Mangano K, et al. Immunomodulatory properties of cefaclor: in vivo effect on cytokine rel

20、ease and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 18(6):641-647,pg/ml,a,33,头孢克洛刺激TNF-的合成,Mangano K, et al. Immunomodulatory properties of cefaclor: in vivo effect on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 18(6):641-647,pg/m

21、l,a,34,头孢克洛刺激IFN-的合成,Mangano K, et al. Immunomodulatory properties of cefaclor: in vivo effect on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 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,*,*,a,35,头孢克洛刺激IFN-的合成,Mangano K, et al. Immunomodulatory properti

22、es of cefaclor: in vivo effect on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 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,*,a,36,头孢克洛刺激IL-2的合成,Mangano K, et al. Immunomodulatory properties of cefaclor: in vivo effect on cytokine release and lymphoproli

23、ferative response in rats. Journal of Chemotherapy 2006, 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,*,a,37,头孢克洛刺激IL-2的合成,Mangano K, et al. Immunomodulatory properties of cefaclor: in vivo effect on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 18(6):64

24、1-647,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,*,*,*,a,38,头孢克洛降低IL-4水平,Mangano K, et al. Immunomodulatory properties of cefaclor: in vivo effect on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 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,*,*,*,

25、a,39,头孢克洛降低IL-4水平,Mangano K, et al. Immunomodulatory properties of cefaclor: in vivo effect on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 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,*,*,*,a,40,头孢克洛降低IL-6水平,Mangano K, et al. Immunomodulatory p

26、roperties of cefaclor: in vivo effect on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 18(6):641-647,pg/ml,a,41,头孢克洛降低IL-6水平,Mangano K, et al. Immunomodulatory properties of cefaclor: in vivo effect on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 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,*,*,*,a,42,头孢克洛刺激IL-10的合成,Mangano K, et