頭孢克洛獨(dú)特的免疫學(xué)特性

1、頭孢克洛獨(dú)特的免疫學(xué)特性,抗生素參與機(jī)體免疫反應(yīng),間接效應(yīng) 直接效應(yīng),間接效應(yīng),殺死細(xì)菌 改變腸道菌群,抗原性 防止細(xì)菌毒素效應(yīng),直接效應(yīng),激活宿主防御機(jī)制(多形核白細(xì)胞) 激活巨噬細(xì)胞吞噬細(xì)胞伸出偽足包圍細(xì)菌并吞入 激活調(diào)理作用激活補(bǔ)體系統(tǒng)，使細(xì)菌易被吞噬并抑制細(xì)菌酶或毒素產(chǎn)生 激活趨化作用使白細(xì)胞向細(xì)菌移動(dòng),影響生物學(xué)效應(yīng)的抗菌藥,對(duì)宿主防御系統(tǒng)無(wú)活性 （一般的內(nèi)酰胺類抗生素） 抑制免疫功能 （四環(huán)素類） 與免疫系統(tǒng)協(xié)同作用 （大環(huán)內(nèi)酯類、喹諾酮類） 增強(qiáng)免疫功能 （某些頭孢烯內(nèi)酰胺類）,影響體外免疫反應(yīng)的抗菌藥,增強(qiáng)吞噬細(xì)胞功能的內(nèi)酰胺類,文獻(xiàn)報(bào)道,?？虅诋?dāng)體外試驗(yàn)敏感，臨床和細(xì)菌學(xué)的療

2、效為95% 當(dāng)體外藥敏耐藥，臨床療效為84%。,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 in the treatment of streptococcal pne

3、umonia 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 and; ower respiratory tract infectio

4、ns 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 open comparative study of azithromy

5、cin 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 children who failed amoxicillin therapy.

6、 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 safety of 5-day cefaclor and 10-day am

7、oxicillin 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. 2003;9(3):P129-35. Catania S, Gallo

8、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 evaluation of cefaclor vs amoxycillin + cl

9、avulanate in children with Acute Otitis Media (AOM). Indian J Pediatr.2005;72(3):233-8.,?？虅谥委熒鐓^(qū)呼吸道感染臨床療效值得信賴,94,97,98,97,96,98,98,90,94,臨床有效率,為什么體外藥敏部分細(xì)菌對(duì)?？虅诓幻舾?，但治療后的臨床療效卻很好？,頭孢克洛的免疫調(diào)節(jié)作用,體外研究,?？虅诰哂畜w內(nèi)增效抗菌特性,Ref:J Chemother,1998;10(2):91-96 .,在人體內(nèi),?？虅谂c中性白細(xì)胞的相互作用,使希刻勞抗菌活性顯著加強(qiáng)（ 對(duì)于肺炎鏈球菌的MBC僅為原來(lái)1/8）,加入中性粒

10、細(xì)胞前,加入中性粒細(xì)胞后,MBC降低 到1/8,頭孢克洛對(duì)金葡菌體內(nèi)外療效比較(第一組),希刻勞具有體內(nèi)增效抗菌特性,頭孢克羅對(duì)金葡菌體內(nèi)及體外療效比較(第二組),?？虅诰哂畜w內(nèi)增效抗菌特性,希刻勞體內(nèi)療效明顯大于體外藥敏試驗(yàn),實(shí)驗(yàn)表明：?？虅趯?duì)革蘭氏陽(yáng)性菌體外的MBC要明顯大于體內(nèi), 頭孢克洛可增強(qiáng)吞噬細(xì)胞的趨化及氧化作用。 頭孢克洛可抑制白細(xì)胞合成丙三烯，抑制氧自由基形成和組胺釋放。,艾效曼,趙瑩,張秀珍.頭孢克洛免疫調(diào)節(jié)功能體外實(shí)驗(yàn),頭孢克洛對(duì)流感嗜血桿菌體內(nèi)和體外模擬試驗(yàn),?？虅诰哂畜w內(nèi)增效抗菌特性,頭孢克洛對(duì)卡他莫拉菌菌體內(nèi)和體外模擬試驗(yàn),希刻勞具有體內(nèi)增效抗菌特性,實(shí)驗(yàn)表明：?？虅?/p>

11、對(duì)革蘭氏陰性菌體外的MBC要明顯大于體內(nèi), 頭孢克洛可增強(qiáng)吞噬細(xì)胞的趨化及氧化作用。 頭孢克洛可抑制白細(xì)胞合成丙三烯，抑制氧自由基形成和組胺釋放。,艾效曼，胡云建，張秀珍修改.頭孢克洛對(duì)流感嗜血桿菌和卡他莫拉菌體內(nèi)模擬實(shí)驗(yàn),希刻勞體內(nèi)療效明顯大于體外藥敏試驗(yàn),頭孢克洛體內(nèi)模擬試驗(yàn)MBC值比較ug/ml,?？虅隗w內(nèi)療效明顯大于體外藥敏試驗(yàn),頭孢克洛對(duì)細(xì)胞因子的免疫調(diào)節(jié)作用,體內(nèi)研究,感染引起的全身炎癥反應(yīng)及隨后機(jī)體的代償性抗炎癥反應(yīng)是導(dǎo)致臟器功能損傷的主要原因,Sergio Zanotti,Sseem Kumar,Anand Kumar,Cytokine modulation in sepsis

12、 and septic shock.Expert Opin Investig.Drugs 2002,11(8):1061-1075,細(xì)菌感染治療結(jié)果的決定因素,藥物的抗菌作用,宿主的免疫功能,+,通過(guò)體外藥敏試驗(yàn)來(lái)判斷,通過(guò)免疫功能測(cè)定 先天免疫 獲得性免疫,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

13、):641-647,有些抗菌藥具有免疫調(diào)節(jié)作用,抗生素對(duì)宿主先天免疫和獲得性免疫的作用可能影響治療結(jié)果 頭孢地嗪免疫調(diào)節(jié)作用最大 頭孢噻肟有免疫抑制作用 頭孢克洛也具有免疫調(diào)節(jié)作用 體外增強(qiáng)粒細(xì)胞的吞噬作用和殺菌活性 體外增強(qiáng)巨噬細(xì)胞的吞噬作用和殺菌活性 體外增強(qiáng)多形核中性粒細(xì)胞(PMN)的活性 可能對(duì)免疫細(xì)胞因子也有調(diào)節(jié)作用,免疫指數(shù)定義,頭孢克洛的免疫調(diào)節(jié)作用可影響機(jī)體免疫防御機(jī)制,?？虅诒蛔C實(shí)有提高機(jī)體免疫反應(yīng)的作用, 抗生素能提高機(jī)體的細(xì)胞免疫和體液免疫。 抗生素能降低細(xì)菌的毒力因子或使其更易被免疫攻擊。 抗生素能幫助機(jī)體免疫功能的恢復(fù)。,1、 JM.T. HAMILTON-MILLE

14、R Department of MedicalMicrobiology, Royal Free and University College Medical School. London, U.K. Immunopharmacology of Antibiotics:Direct and Indirect Immunomodulation of Defence Mechanisms LEADING ARTICLE Journal of chemotherapy Vol 2001;13(2):107-111,頭孢克洛對(duì)免疫的調(diào)節(jié)作用,動(dòng)物試驗(yàn),Mangano K, et al. Immunomo

15、dulatory properties of cefaclor: in vivo effect on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 18(6):641-647,細(xì)胞因子與免疫功能,I型細(xì)胞因子：促炎癥細(xì)胞因子 IFN-、TNF-、IL-1、IL-2、IL-12、IL-18 刺激細(xì)胞介導(dǎo)的免疫效應(yīng)細(xì)胞，如巨噬細(xì)胞、細(xì)胞毒性T細(xì)胞以及NK細(xì)胞 上調(diào)遲發(fā)型超敏反應(yīng) 調(diào)節(jié)免疫，參與清除胞內(nèi)病原體 2型細(xì)胞因子 IL-4、IL-5、IL-6、IL-10、IL

16、-13 主要調(diào)節(jié)體液免疫應(yīng)答，刺激IgG1和IgE的生成 下調(diào)巨噬細(xì)胞、細(xì)胞毒性T細(xì)胞以及NK細(xì)胞的功能活性 3型細(xì)胞因子 TGF- 主要調(diào)節(jié)體液免疫應(yīng)答，刺激IgG1和IgE的生成 下調(diào)巨噬細(xì)胞、細(xì)胞毒性T細(xì)胞以及NK細(xì)胞的功能活性,實(shí)驗(yàn)方法,大鼠口服頭孢克洛 劑量是10、50或100mg/kg/d 療程3天或6天 對(duì)照組口服磷酸鹽緩沖液(PBS) 吸入CO2處死動(dòng)物 取動(dòng)物脾臟，制備細(xì)胞懸液 進(jìn)行免疫試驗(yàn) 淋巴細(xì)胞增殖試驗(yàn) 測(cè)定各種細(xì)胞因子水平,Mangano K, et al. Immunomodulatory properties of cefaclor: in vivo effect

17、 on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 18(6):641-647,主要結(jié)果,頭孢克洛刺激淋巴細(xì)胞增殖,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

18、-647,細(xì)胞增殖指數(shù),P=0.001,P=0.001,P=0.002,P=0.045,*P值是與頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果,P=0.002,頭孢克洛刺激淋巴細(xì)胞增殖,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,細(xì)胞增殖指數(shù),P0.001,P0.001,P0.001,P=0

19、.001,P=0.001,P=0.004,*P值是與頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果,頭孢克洛刺激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/ml,頭孢克洛刺激TNF-的合成,Mangano K, et al. Immunomodulatory proper

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

21、al of Chemotherapy 2006, 18(6):641-647,pg/ml,*P0.001，頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果,*,*,頭孢克洛刺激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，頭孢克洛組與賦形劑組相比t檢驗(yàn)的

22、結(jié)果,*,頭孢克洛刺激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):641-647,pg/ml,*P=0.001，頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果,*,頭孢克洛刺激IL-2的合成,Mangano K, et al. Immunomodulatory properties of ce

23、faclor: in vivo effect on cytokine release and lymphoproliferative response in rats. Journal of Chemotherapy 2006, 18(6):641-647,pg/ml,*P0.001，*p=0.007，頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果,*,*,*,頭孢克洛降低IL-4水平,Mangano K, et al. Immunomodulatory properties of cefaclor: in vivo effect on cytokine release and lymphoprolif

24、erative response in rats. Journal of Chemotherapy 2006, 18(6):641-647,pg/ml,*P0.001，*p=0.003，頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果,*,*,*,頭孢克洛降低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(

25、6):641-647,pg/ml,*P0.001，*p=0.001，頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果,*,*,*,頭孢克洛降低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,頭孢克洛降低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，頭孢克洛組與賦形劑組相比t檢驗(yàn)的結(jié)果,*,*,*,頭孢克洛刺激IL-10的合成,Mangano K,