Hockertz S, Heckenberger R, Emmendörffer A, Müller M
Fraunhofer Institute for Toxicology, Department of Immunology, Hannover, Fed. Rep. of Germany.
Arzneimittelforschung. 1995 Jan;45(1):104-7.
Listeria monocytogenes is a bacterial infection, which is facultatively localized in monocytes and macrophages. The influence of ibuprofen (CAS 15687-27-1), a nonsteroidal anti-inflammatory drug (NSAID), on this bacterial infection in balb/c mice was investigated. One day prior to sublethal infection, balb/c mice were treated intravenously with various therapeutic concentrations of ibuprofen alone or ibuprofen in combination with a suboptimal dosage of murine recombinant interferon gamma, a lymphokine produced by T-helper cells. Three days post-infection, parasite burdens of the mainly infected organs, spleen and liver, were determined by the colony-forming unit assay. It was shown that the prophylactic treatment with ibuprofen in a concentration of 4 mg/kg body weight resulted in a more than 10-fold reduction of viable Listeria monocytogenes in the spleen, whereas in liver 12 mg/kg Ibuprofen was necessary for a comparable kill of viable bacteria. A higher concentration of ibuprofen did not resulted in a higher antibacterial efficacy. In order to clarify the mechanism of ibuprofen action, molecular-biological experiments were performed to measure the messenger RNA (mRNA) induced by ibuprofen. It is presented here that therapeutic concentrations of ibuprofen induced significant higher amounts of mRNA for interleukin-1 in human monocytes compared to untreated cells. These findings support the hypothesis that ibuprofen influences the complex immune system to overcome a bacterial infection.
单核细胞增生李斯特菌是一种细菌感染，它可兼性定位于单核细胞和巨噬细胞中。研究了非甾体抗炎药（NSAID）布洛芬（CAS 15687-27-1）对balb/c小鼠这种细菌感染的影响。在亚致死感染前一天，给balb/c小鼠静脉注射各种治疗浓度的布洛芬，单独使用或与次优剂量的小鼠重组干扰素γ（一种由辅助性T细胞产生的淋巴因子）联合使用。感染后三天，通过菌落形成单位测定法确定主要感染器官脾脏和肝脏中的寄生虫负荷。结果表明，以4mg/kg体重的浓度预防性使用布洛芬可使脾脏中存活的单核细胞增生李斯特菌减少10倍以上，而在肝脏中，需要12mg/kg布洛芬才能达到类似的杀灭存活细菌的效果。更高浓度的布洛芬并未产生更高的抗菌效果。为了阐明布洛芬的作用机制，进行了分子生物学实验以测量布洛芬诱导的信使核糖核酸（mRNA）。结果表明，与未处理的细胞相比，治疗浓度的布洛芬在人单核细胞中诱导产生的白细胞介素-1的mRNA量显著更高。这些发现支持了布洛芬影响复杂的免疫系统以克服细菌感染这一假说。
