Gürer Umran Soyoğul, Göçer Pervin, Erçağ Erol, Erten Nilgün, Rayaman Erkan, Gürbüz Burçak, Uzer Ayşem, Karan Akif, Cevikbaş Adile
Department of Pharmaceutical Microbiology, Faculty of Pharmacy, University of Marmara, Haydarpasa, Istanbul, Turkey.
Int Immunopharmacol. 2006 May;6(5):808-16. doi: 10.1016/j.intimp.2005.12.001. Epub 2005 Dec 27.
The effects of ciprofloxacin, cefodizime, rifampicine, doxycycline and cefodizime + rifampicine combination on polymorphonuclear leukocyte (PMN) functions (phagocytosis and intracellular killing activity) were investigated in vitro in elderly patients and compared with those of healthy young volunteers before and after zinc supplementation. PMNs of 13 elderly hypertensive patients and 10 healthy young volunteers were isolated by Ficoll-Hypaque gradient centrifugation method from venous blood with EDTA. The subjects were given 22 mg/daily/oral zinc supplementation for 1 month. Serum zinc levels before and after supplementation were measured by flame atomic absorbtion spectrophotometer and the effects of each drug on PMN functions at therapeutic concentrations were investigated. Ciprofloxacin significantly increased the PMN's phagocytic activity of elderly patients (p = 0.002) before zinc supplementation and significantly increased both PMN functions of elderly patients (p = 0.002) after zinc supplementation. The same antibiotic significantly increased both PMN functions of healthy young volunteers (p = 0.005 and p<0.05, respectively) before and after zinc supplementation when compared with the control (drug-free). Cefodizime significantly increased the PMN's phagocytic activity of elderly patients (p = 0.003, p = 0.002) before and after zinc supplementation when compared with the control (drug-free). It also significantly increased both PMN functions of healthy young volunteers (p = 0.005 and p<0.05, respectively) before and after zinc supplementation when compared with the control (drug-free). Doxycycline significantly increased PMN's intracellular killing activity of healthy young volunteers before zinc supplementation (p<0.05) when compared with the control (drug-free) values. Rifampicine significantly decreased PMN's phagocytic activity of elderly patients (p<0.05) after zinc supplementation. Cefodizime+rifampicine combination significantly increased PMN's phagocytic activity at therapeutic concentrations of healthy young volunteers (p = 0.005) before zinc supplementation and PMN's phagocytic activity of elderly patients (p<0.05) after zinc supplementation when compared with the control (drug-free). Consequently, in the present study from the antibiotics ciprofloxacin, cefodizime and cefodizime + rifampicine combination, which are accepted as biological response modifiers have demonstrated stimulatory effects by significantly increasing polymorphonuclear leucocyte functions (phagocytosis and/or intracellular killing activity) of elderly patients and healthy young volunteers in vitro before and after zinc supplementation. Additionally zinc supplementation has more immunostimulatory effects on PMN functions of healthy young volunteers than elderly patients.
在老年患者中,体外研究了环丙沙星、头孢地嗪、利福平、强力霉素以及头孢地嗪+利福平组合对多形核白细胞(PMN)功能(吞噬作用和细胞内杀伤活性)的影响,并与补充锌前后的健康年轻志愿者进行比较。通过Ficoll-Hypaque梯度离心法从含乙二胺四乙酸(EDTA)的静脉血中分离出13名老年高血压患者和10名健康年轻志愿者的PMN。受试者每天口服22毫克锌,持续1个月。采用火焰原子吸收分光光度计测量补充锌前后的血清锌水平,并研究每种药物在治疗浓度下对PMN功能的影响。环丙沙星在补充锌前显著提高了老年患者PMN的吞噬活性(p = 0.002),在补充锌后显著提高了老年患者的两种PMN功能(p = 0.002)。与对照组(无药物)相比,相同抗生素在补充锌前后均显著提高了健康年轻志愿者的两种PMN功能(分别为p = 0.005和p<0.05)。与对照组(无药物)相比,头孢地嗪在补充锌前后均显著提高了老年患者PMN的吞噬活性(p = 0.003,p = 0.002)。与对照组(无药物)相比,它在补充锌前后也显著提高了健康年轻志愿者的两种PMN功能(分别为p = 0.005和p<0.05)。与对照组(无药物)的值相比,强力霉素在补充锌前显著提高了健康年轻志愿者PMN的细胞内杀伤活性(p<0.05)。利福平在补充锌后显著降低了老年患者PMN的吞噬活性(p<0.05)。与对照组(无药物)相比,头孢地嗪+利福平组合在补充锌前对健康年轻志愿者在治疗浓度下显著提高了PMN的吞噬活性(p = 0.005),在补充锌后显著提高了老年患者PMN的吞噬活性(p<0.05)。因此,在本研究中,被认为是生物反应调节剂的抗生素环丙沙星、头孢地嗪以及头孢地嗪+利福平组合,在体外补充锌前后均通过显著提高老年患者和健康年轻志愿者的多形核白细胞功能(吞噬作用和/或细胞内杀伤活性)而表现出刺激作用。此外,补充锌对健康年轻志愿者PMN功能比老年患者具有更强的免疫刺激作用。