title: The cardiac glycoside digoxin disrupts host defense in experimental pneumococcal pneumonia by impairing neutrophil mobilization.
abstract: Normal CD-1 mice were administered digoxin (4 micrograms/kg/24 h) and infected with type 3 Streptococcus pneumoniae in order to assess the effects of the cardiac glycoside on the chemotactic responsiveness of peripheral blood neutrophils and the mobilization of granulocytes from storage pools. The chemotactic responses to autologous zymosan-activated serum (C5a) by neutrophils obtained from uninfected digoxin-treated and control animals were similar; comparable observations were made with circulating granulocytes isolated from animals at 24 or 48 h after intratracheal challenge with 5 x 10(5) colony-forming units (cfu) of bacteria. However, at 4 and 6 h after intratracheal pneumococcal challenge, the number of immature neutrophils in the peripheral blood was significantly lower in the glycoside-treated animals versus controls; at 24 and 48 h, these differences were not apparent. Following the intravenous inoculation of pneumococci, the number of circulating immature neutrophils was also found to be significantly lower at 4 and 24 h in animals given the cardiac glycoside versus controls. We conclude that digoxin disrupts host defense in experimental pneumococcal pneumonia and bacteremia by impairing the mobilization of neutrophils.
authors.affiliation: Department of Medicine, Boston University Medical Center, MA.
authors.forename: A L
authors.initials: AL
authors.lastname: Esposito
authors.forename: W J
authors.initials: WJ
authors.lastname: Poirier
authors.forename: C A
authors.initials: CA
authors.lastname: Clark
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004077:Digoxin / Q000633:toxicity*; D005260:Female; D005856:Germ-Free Life; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000097:blood / Q000276:immunology*
chemical_list: D004077:Digoxin