Chloroquine enhances survival in Bacillus anthracis intoxication.
The intentional release of anthrax in the United States in 2001 resulted in 11 cases of inhalational disease, with an attendant mortality rate of 45%. Current therapeutic options for anthrax are limited; antimicrobials target only replicating organisms, thus allowing bacterial toxins to cause unchecked, devastating physiological derangements in the host. Novel approaches that target the cytotoxic effects of anthrax exotoxins are needed. Chloroquine (CQ), a commonly used antimalarial agent, endows anthrax-intoxicated murine peritoneal macrophages with a 50% and 35% marginal survival advantage at 2 and 4 h, respectively, over that of untreated control cells. The cell rescue is dose dependent and, at lower concentrations, results in delayed cell death. We subsequently studied the effect of CQ in BALB/c mice challenged with anthrax lethal toxin. CQ-treated mice demonstrated reduced tissue injury, as assessed by histopathological examination of the spleen and by peripheral blood differential cell count ratios. CQ significantly enhanced survival and may augment current treatment and prophylaxis options for this otherwise lethal infection.
Artenstein
Andrew W
AW
Center for Biodefense and Emerging Pathogens, Division of Infectious Diseases, Memorial Hospital of Rhode Island, Pawtucket 02860, USA. artenstein@brown.edu.
Opal
Steven M
SM
Cristofaro
Patricia
P
Palardy
John E
JE
Parejo
Nicolas A
NA
Green
Michael D
MD
Jhung
Jhung W
JW
D000818:Animals; D000881:Anthrax / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D000942:Antigens, Bacterial / Q000633:toxicity*; D001408:Bacillus anthracis / Q000187:drug effects / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002738:Chloroquine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007958:Leukocyte Count; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes; D009504:Neutrophils; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000473:pathology; D016019:Survival Analysis
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D002738:Chloroquine