Bacillus anthracis cell wall produces injurious inflammation but paradoxically decreases the lethality of anthrax lethal toxin in a rat model.
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.
Cui
Xizhong
X
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Building 10, Room 2C148, Bethesda, MD 20892, USA.
Su
Junwu
J
Li
Yan
Y
Shiloach
Joseph
J
Solomon
Steven
S
Kaufman
Jeanne B
JB
Mani
Haresh
H
Fitz
Yvonne
Y
Weng
Jia
J
Altaweel
Laith
L
Besch
Virginia
V
Eichacker
Peter Q
PQ
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
D001427:Bacterial Toxins