Intensive Care Medicine

, Volume 36, Issue 1, pp 148–156

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

  • Xizhong Cui
  • Junwu Su
  • Yan Li
  • Joseph Shiloach
  • Steven Solomon
  • Jeanne B. Kaufman
  • Haresh Mani
  • Yvonne Fitz
  • Jia Weng
  • Laith Altaweel
  • Virginia Besch
  • Peter Q. Eichacker
Experimental

DOI: 10.1007/s00134-009-1643-9

Cite this article as:
Cui, X., Su, J., Li, Y. et al. Intensive Care Med (2010) 36: 148. doi:10.1007/s00134-009-1643-9

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 

Supplementary material

134_2009_1643_MOESM1_ESM.pdf (584 kb)
Supplementary material (PDF 215 kb)

Copyright information

© Copyright jointly hold by Springer and ESICM 2009

Authors and Affiliations

  • Xizhong Cui
    • 1
  • Junwu Su
    • 1
  • Yan Li
    • 1
  • Joseph Shiloach
    • 2
  • Steven Solomon
    • 1
  • Jeanne B. Kaufman
    • 2
  • Haresh Mani
    • 3
  • Yvonne Fitz
    • 1
  • Jia Weng
    • 1
  • Laith Altaweel
    • 1
  • Virginia Besch
    • 4
  • Peter Q. Eichacker
    • 1
  1. 1.Critical Care Medicine Department, Clinical CenterNational Institutes of HealthBethesdaUSA
  2. 2.NIDDK, National Institutes of HealthBethesdaUSA
  3. 3.Laboratory of PathologyNational Cancer Institutes, National Institutes of HealthBethesdaUSA
  4. 4.Department of AnesthesiologyClinical Center, National Institutes of HealthBethesdaUSA

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