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Digoxin disrupts the inflammatory response in experimental pneumococcal pneumonia
Abstract:
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.
Insights
Digoxin impairs lung antibacterial defenses against Streptococcus pneumoniae, worsening survival rates in mice. This cardiac glycoside disrupts the inflammatory response and immune cell recruitment needed to clear bacterial infections.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Cardiac glycosides like digoxin are used to treat heart conditions.
- The impact of digoxin on pulmonary antibacterial mechanisms is not well understood.
- Streptococcus pneumoniae is a common cause of bacterial pneumonia.
Purpose of the Study:
- To investigate the effects of digoxin on pulmonary antibacterial mechanisms against Streptococcus pneumoniae.
- To determine if digoxin influences the host's ability to clear pneumococcal infections in the lungs.
Main Methods:
- Normal CD-1 mice were administered digoxin.
- Mice were intratracheally inoculated with Streptococcus pneumoniae.
- Pulmonary clearance of viable pneumococci and immune cell recruitment (granulocytes and macrophages) were assessed.
- In vitro pneumococcidal activity of alveolar macrophages was evaluated.
Main Results:
- Digoxin treatment significantly reduced mouse survival rates compared to controls.
- Digoxin impaired the clearance of viable pneumococci from the lungs.
- A marked attenuation in the recruitment of granulocytes and macrophages into bronchoalveolar spaces was observed in digoxin-treated mice.
- Digoxin did not affect the in vitro killing of pneumococci by alveolar macrophages at clinically relevant concentrations.
Conclusions:
- Digoxin disrupts host defense against Streptococcus pneumoniae by impeding the inflammatory response in the lungs.
- The cardiac glycoside interferes with the recruitment of immune cells necessary for clearing bacterial infections.
- Digoxin's negative impact on pulmonary antibacterial mechanisms warrants further investigation, especially in patients with pneumonia.