Digoxin disrupts the inflammatory response in experimental pneumococcal pneumonia.

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.