Delayed treatment with doxycycline has limited effect on anthrax infection in BLK57/B6 mice.
Blk57/B6 mice were infected with LD90 dose of Sterne strain anthrax spores subcutaneously and then treated with doxycycline. Doxycycline at a dose of 1.5mg/kg, by intra-peritoneal injection, protected mice from death when given at the same time as spores. When doxycycline administration was delayed 4h survival is 90%. Delay of 24h increased survival time but had no impact on eventual mortality. When doxycycline was delayed 48h, mortality and time to death were comparable to sham injection. Peritoneal macrophages harvested from Blk57/B6 mice were examined for response to anthrax lethal toxin and are shown to be deficient in their ability to produce TNF-alpha and have increased expression of IL-6 compared to RAW 264.7 murine macrophage cell line. These findings suggest that antibiotic therapy has limited effects following lethal anthrax spore challenge, even when the host is of a phenotype that does not produce TNF-alpha in response to anthrax lethal toxin exposure.
Kalns
John
J
Davis Hyperbaric Laboratory, USAFSAM/FEH, 2602 Louis Bauer Drive, Brooks City-Base, TX 78235-5252, USA. john.kalns@brooks.af.mil
Morris
Julie
J
Eggers
Jeffrey
J
Kiel
Johnathan
J
D000818:Animals; D000881:Anthrax / Q000188:drug therapy*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001408:Bacillus anthracis; D002460:Cell Line; D004318:Doxycycline / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013171:Spores, Bacterial; D016019:Survival Analysis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000900:Anti-Bacterial Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D004318:Doxycycline