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Bacillus anthracis cell wall produces injurious inflammation but paradoxically decreases the lethality of anthrax lethal toxin in a rat model
Objectives 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). Method and Results Sprague–Dawley rat...
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Published in: | Intensive care medicine 2010-01, Vol.36 (1), p.148-156 |
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Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Objectives
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).
Method and 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
≤ 0.05). Changes with lethal doses were greater than changes with nonlethal doses (
P
≤ 0.01). Lethal bolus or infusion doses produced hypotension or hypoxemia, respectively (
P
≤ 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
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ISSN: | 0342-4642 1432-1238 |
DOI: | 10.1007/s00134-009-1643-9 |