Siedlar M, Szczepanik A, Wieckiewicz J, Pituch-Noworolska A, Zembala M
Department of Clinical Immunology, Polish-American Children Hospital, Medical Faculty, Jagiellonian University, Cracow, Poland.
Immunopharmacology. 1997 Jan;35(3):265-71. doi: 10.1016/s0162-3109(96)00156-7.
The cytokines play an important role in the cascade of the pathological events leading to septic shock. The TNF alpha produced by monocytes/macrophages upon stimulation with bacterial fragments may contribute to induction of this cytokine cascade. Moreover, the antibiotics used for antimicrobial therapy may cause the increase of TNF alpha production due to massive bacterial killing and exposure of monocytes/macrophages to bacterial cell constituents. To investigate the effect of Vancomycin on TNF alpha production, an in vitro model of LPS-stimulated monocytes was used. The level of TNF alpha protein or TNF biological activity were tested in the culture supernatants of monocytes with LPS. Vancomycin down-regulated, in dose-dependent manner, the TNF alpha production. Vancomycin also inhibited TNF alpha-mRNA accumulation in LPS-stimulated monocytes, as assessed by fluorescence in situ hybridization (FISH) in cell suspension. The down-regulation of TNF alpha production in LPS-stimulated monocytes may indicate that inhibition of this cytokine release is one of the important therapeutic effects of Vancomycin in sepsis.
细胞因子在导致脓毒性休克的一系列病理事件中起重要作用。单核细胞/巨噬细胞在受到细菌片段刺激后产生的肿瘤坏死因子α（TNFα）可能有助于引发这种细胞因子级联反应。此外，用于抗菌治疗的抗生素可能由于大量杀灭细菌以及单核细胞/巨噬细胞接触细菌细胞成分而导致TNFα产生增加。为了研究万古霉素对TNFα产生的影响，使用了脂多糖（LPS）刺激单核细胞的体外模型。在LPS刺激的单核细胞培养上清液中检测TNFα蛋白水平或TNF生物学活性。万古霉素以剂量依赖的方式下调TNFα的产生。通过细胞悬液中的荧光原位杂交（FISH）评估，万古霉素还抑制LPS刺激的单核细胞中TNFα - mRNA的积累。LPS刺激的单核细胞中TNFα产生的下调可能表明抑制这种细胞因子释放是万古霉素在脓毒症中的重要治疗作用之一。
