Matera G, Berlinghieri M C, Foti F, Barreca G S, Focà A
Department of Microbiological, Neurological and Orthopaedic Sciences, University of Reggio Calabria, Cantanzaro, Italy.
J Antimicrob Chemother. 1996 Nov;38(5):799-807. doi: 10.1093/jac/38.5.799.
The way in which an antibiotic interacts with host defences could influence the clinical outcome of many infectious diseases. The impact of RO 23-9424, a novel dual-action and extended-spectrum antibiotic, was studied on several functions of human polymorphonuclear neutrophils (PMNs). A significant (P < 0.05) increase of the superoxide (O2-) released by phorbol-myristate acetate (PMA) -stimulated PMN (10-100 mg/L) can be observed in the RO 23-9424 pre-treated cells. RO 23-9424, particularly at low dosages, showed an interesting but not statistically significant effect on PMN phagocytosis. Higher dosages of RO 23-9424 (50-200 mg/L) and fleroxacin (20-200 mg/L) significantly reduced PMN chemotaxis. Cytokine production by human monocytes were also evaluated after incubation with the antibiotic (100-200 mg/L) in both basal conditions and in response to endotoxin (lipopolysaccharide, LPS). In the LPS-treated cells, RO 23-9424 (100 mg/L) significantly (P < 0.05) enhanced the tumour necrosis factor-alpha (TNF-alpha) levels, compared with LPS controls after 4 h of incubation. RO 23-9424 (200 mg/L) was able to reduce in a dose-dependent way LPS-induced interleukin-1 beta (IL-1 beta) after 4 and 24 h of incubation. Interleukin-8 (IL-8) release was not significantly changed by RO 23-9424. Cefotaxime (200 mg/L) significantly (P < 0.05) increased the basal levels of IL-1 beta and reduced basal IL-8 concentration after 24 h of incubation. The lower concentration of cefotaxime reduced the LPS-stimulated IL-8 levels. Fleroxacin (100 mg/L) enhanced basal levels of IL-8. The potentiated PMN phagocytosis, the significantly enhanced O2- release by PMA-stimulated PMN and the dimetric changes of TNF-alpha and IL-1 beta appeared peculiar for RO 23-9424 and may have useful therapeutical implications.
抗生素与宿主防御机制相互作用的方式可能会影响许多传染病的临床结果。我们研究了新型双效广谱抗生素RO 23-9424对人多形核中性粒细胞（PMN）多种功能的影响。在经RO 23-9424预处理的细胞中，可观察到佛波酯-肉豆蔻酸酯乙酸酯（PMA）刺激的PMN（10-100 mg/L）释放的超氧化物（O2-）显著（P < 0.05）增加。RO 23-9424，尤其是低剂量时，对PMN吞噬作用显示出有趣但无统计学意义的影响。较高剂量的RO 23-9424（50-200 mg/L）和氟罗沙星（20-200 mg/L）显著降低PMN趋化性。在基础条件下以及对内毒素（脂多糖，LPS）反应时，将抗生素（100-200 mg/L）与人单核细胞孵育后，也评估了细胞因子的产生。在LPS处理的细胞中，孵育4小时后，与LPS对照相比，RO 23-9424（100 mg/L）显著（P < 0.05）提高了肿瘤坏死因子-α（TNF-α）水平。孵育4小时和24小时后，RO 23-9424（200 mg/L）能够以剂量依赖性方式降低LPS诱导的白细胞介素-1β（IL-1β）。RO 23-9424对白细胞介素-8（IL-8）释放没有显著影响。头孢噻肟（200 mg/L）孵育24小时后显著（P < 0.05）提高了IL-1β的基础水平并降低了基础IL-8浓度。较低浓度的头孢噻肟降低了LPS刺激的IL-8水平。氟罗沙星（100 mg/L）提高了IL-8的基础水平。RO 23-9424所具有的增强的PMN吞噬作用、PMA刺激的PMN显著增强的O2-释放以及TNF-α和IL-1β的双向变化似乎很独特，可能具有有益的治疗意义。
