title: Bacillus anthracis cell wall produces injurious inflammation but paradoxically decreases the lethality of anthrax lethal toxin in a rat model.
abstract: OBJECTIVE
  The in vivo inflammatory effects of the Bacillus anthracis cell wall are unknown. We therefore investigated these effects in rats and, for comparison, those of known inflammatory stimulants, Staphylococcus aureus cell wall or lipopolysaccharide (LPS).
  
  
  RESULTS
  Sprague-Dawley rats (n = 103) were challenged with increasing B. anthracis cell wall doses (10, 20, 40, 80, or 160 mg/kg) or diluent (control) as a bolus or 24-h infusion. The three highest bolus doses were lethal (20-64% lethality rates) as were the two highest infused doses (13% with each). Comparisons among lethal or nonlethal doses on other measured parameters were not significantly different, and these were combined for analysis. Over the 24 h after challenge initiation with lethal bolus or infusion, compared to controls, ten inflammatory cytokines and NO levels were increased and circulating neutrophils and platelets decreased (P <or= 0.05). Changes with lethal doses were greater than changes with nonlethal doses (P <or= 0.01). Lethal bolus or infusion doses produced hypotension or hypoxemia, respectively (P <or= 0.05). The effects with B. anthracis cell wall were similar to those of S. aureus cell wall or LPS. However, paradoxically administration of B. anthracis cell wall or LPS decreased the lethality of concurrently administered B. anthracis lethal toxin (P < 0.0001 and 0.04, respectively).
  
  
  CONCLUSIONS
  B. anthracis cell wall has the potential to produce inflammatory injury during anthrax infection clinically. However, understanding why cell wall or LPS paradoxically reduced lethality with lethal toxin may help understand this toxin's pathogenic effects.
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Building 10, Room 2C148, Bethesda, MD 20892, USA.
authors.forename: Xizhong
authors.initials: X
authors.lastname: Cui
authors.forename: Junwu
authors.initials: J
authors.lastname: Su
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Joseph
authors.initials: J
authors.lastname: Shiloach
authors.forename: Steven
authors.initials: S
authors.lastname: Solomon
authors.forename: Jeanne B
authors.initials: JB
authors.lastname: Kaufman
authors.forename: Haresh
authors.initials: H
authors.lastname: Mani
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Fitz
authors.forename: Jia
authors.initials: J
authors.lastname: Weng
authors.forename: Laith
authors.initials: L
authors.lastname: Altaweel
authors.forename: Virginia
authors.initials: V
authors.lastname: Besch
authors.forename: Peter Q
authors.initials: PQ
authors.lastname: Eichacker
mesh_terms: D000818:Animals; D001408:Bacillus anthracis / Q000378:metabolism* / Q000472:pathogenicity*; D001424:Bacterial Infections / Q000378:metabolism* / Q000473:pathology*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D001792:Blood Platelets / Q000378:metabolism / Q000382:microbiology; D002473:Cell Wall / Q000382:microbiology; D004195:Disease Models, Animal; D053208:Kaplan-Meier Estimate; D008214:Lymphocytes / Q000378:metabolism / Q000382:microbiology; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013211:Staphylococcus aureus / Q000378:metabolism / Q000472:pathogenicity; D013997:Time Factors
chemical_list: D001427:Bacterial Toxins