Experimental

Intensive Care Medicine

, Volume 36, Issue 1, pp 148-156

First online:

Bacillus anthracis cell wall produces injurious inflammation but paradoxically decreases the lethality of anthrax lethal toxin in a rat model

  • Xizhong CuiAffiliated withCritical Care Medicine Department, Clinical Center, National Institutes of Health
  • , Junwu SuAffiliated withCritical Care Medicine Department, Clinical Center, National Institutes of Health
  • , Yan LiAffiliated withCritical Care Medicine Department, Clinical Center, National Institutes of Health
  • , Joseph ShiloachAffiliated withNIDDK, National Institutes of Health
  • , Steven SolomonAffiliated withCritical Care Medicine Department, Clinical Center, National Institutes of Health
  • , Jeanne B. KaufmanAffiliated withNIDDK, National Institutes of Health
  • , Haresh ManiAffiliated withLaboratory of Pathology, National Cancer Institutes, National Institutes of Health
  • , Yvonne FitzAffiliated withCritical Care Medicine Department, Clinical Center, National Institutes of Health
  • , Jia WengAffiliated withCritical Care Medicine Department, Clinical Center, National Institutes of Health
    • , Laith AltaweelAffiliated withCritical Care Medicine Department, Clinical Center, National Institutes of Health
    • , Virginia BeschAffiliated withDepartment of Anesthesiology, Clinical Center, National Institutes of Health
    • , Peter Q. EichackerAffiliated withCritical Care Medicine Department, Clinical Center, National Institutes of Health Email author 

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Abstract

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 < 0.0001 and 0.04, respectively).

Conclusion

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.

Keywords

Bacillus anthracis Cell wall Cardiopulmonary dysfunction Cytokine release Inflammation