Esposito A L
J Infect Dis. 1985 Jul;152(1):14-23. doi: 10.1093/infdis/152.1.14.
Digoxin was administered to normal CD-1 mice (4 micrograms/kg per 24 hr), and the mice were inoculated intratracheally with Streptococcus pneumoniae in order to assess the effects of the cardiac glycoside on pulmonary antibacterial mechanisms. Digoxin-treated animals experienced a worse survival rate than did controls (19 of 50 versus 33 of 50; P less than .01). When challenged with a high inoculum (1 X 10(6) cfu), animals given the glycoside demonstrated a significant impairment in their capacity to clear viable pneumococci from the lungs; the depression in pulmonary clearance was associated with a marked attenuation in the ability of digoxin-treated mice to recruit granulocytes and macrophages into the bronchoalveolar spaces. Following low inoculum challenge (1 X 10(5) cfu), animals treated with the cardiac glycoside exhibited an inefficient pulmonary clearance and a blunted macrophage influx. At clinically relevant concentrations, digoxin demonstrated no effect on the in vitro pneumococcidal activity of resident murine alveolar macrophages. We conclude that digoxin can disrupt host defense against pneumococcus by impeding the normal inflammatory response to organisms deposited into the lower respiratory tract.
将地高辛给予正常的CD - 1小鼠（每24小时4微克/千克），并经气管内接种肺炎链球菌，以评估强心苷对肺部抗菌机制的影响。接受地高辛治疗的动物存活率低于对照组（50只中有19只存活，而对照组50只中有33只存活；P小于0.01）。当用高接种量（1×10⁶cfu）攻击时，给予强心苷的动物清除肺内活肺炎球菌的能力显著受损；肺部清除功能的降低与地高辛治疗小鼠将粒细胞和巨噬细胞募集到支气管肺泡间隙的能力明显减弱有关。在低接种量攻击（1×10⁵cfu）后，接受强心苷治疗的动物表现出肺部清除效率低下和巨噬细胞流入减少。在临床相关浓度下，地高辛对驻留的小鼠肺泡巨噬细胞的体外杀肺炎球菌活性没有影响。我们得出结论，地高辛可通过阻碍对沉积在下呼吸道的病原体的正常炎症反应来破坏宿主对肺炎球菌的防御。
