Hockertz S, Heckenberger R
Fraunhofer Department of Toxicology and Environmental Medicine, Hamburg.
Arzneimittelforschung. 1996 Oct;46(10):1012-5.
The bacterial infection with Listeria monocytogenes is associated with an inhibition of the macrophage function, the first-line defense against bacterial infection. We studied the effect of acetylsalicylic acid (ASA, CAS 50-78-2) and ibuprofen (CAS 15687-21-1) alone and in combination with a suboptimal dose of recombinant interferon gamma. (IFN gamma) on the acute infection with Listeria monocytogenes in the Balb/c mouse. Animals were intravenously infected with a sublethal dose of Listeria monocytogenes. The therapy was carried out I) at the time of the infection, II) 30 min, III) 60 min, IV) 3 h and V) 24 h post infection. Six groups of mice were treated: i) untreated control, ii) 10(4) units IFN gamma, iii) 10 mg/kg ASA, i.v.) 10 mg/kg ASA + IFN gamma, i.v.) 12 mg/kg ibuprofen, and vi) 12 mg/kg ibuprofen + IFN gamma. The data shown that treatment with ibuprofen and ASA resulted in a significant reduction of viable bacteria in spleen and liver, the main organs of this infection. In combination with low dose interferon gamma, both non-steroidal anti-inflammatory drugs (NSAID) reduced the parasite burden in the examined organs by a factor of more than 10. The therapeutic efficacy showed its maximum 1 h after challenge with Listeria monocytogenes. These results suggest that ibuprofen and ASA possess antibacterial activity. In addition, IFN gamma significantly increases the antibacterial activity of ASA and ibuprofen. Presumably, these effects are due to an influence on the host immune system.
单核细胞增生李斯特菌的细菌感染与巨噬细胞功能受到抑制有关,巨噬细胞是抵御细菌感染的第一道防线。我们研究了乙酰水杨酸(ASA,化学物质登记号50 - 78 - 2)和布洛芬(化学物质登记号15687 - 21 - 1)单独使用以及与次优剂量的重组干扰素γ(IFNγ)联合使用对Balb/c小鼠单核细胞增生李斯特菌急性感染的影响。动物经静脉注射亚致死剂量的单核细胞增生李斯特菌。治疗分别在以下时间进行:I)感染时,II)感染后30分钟,III)感染后60分钟,IV)感染后3小时,V)感染后24小时。将小鼠分为六组进行治疗:i)未治疗的对照组,ii)10⁴单位IFNγ,iii)10mg/kg ASA(静脉注射),iv)10mg/kg ASA + IFNγ(静脉注射),v)12mg/kg布洛芬,vi)12mg/kg布洛芬 + IFNγ。数据显示,使用布洛芬和ASA治疗可使脾脏和肝脏(该感染的主要器官)中的活菌数量显著减少。与低剂量干扰素γ联合使用时,两种非甾体抗炎药(NSAID)均使所检查器官中的寄生虫负荷降低了10倍以上。治疗效果在感染单核细胞增生李斯特菌1小时后达到最大值。这些结果表明布洛芬和ASA具有抗菌活性。此外,IFNγ显著增强了ASA和布洛芬的抗菌活性。推测这些作用是由于对宿主免疫系统的影响。