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

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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.

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Authors and Affiliations

  1. Critical Care Medicine Department, Clinical Center, National Institutes of Health, Building 10, Room 2C148, Bethesda, MD, 20892, USA

    Xizhong Cui, Junwu Su, Yan Li, Steven Solomon, Yvonne Fitz, Jia Weng, Laith Altaweel & Peter Q. Eichacker

  2. NIDDK, National Institutes of Health, Bethesda, MD, 20892, USA

    Joseph Shiloach & Jeanne B. Kaufman

  3. Laboratory of Pathology, National Cancer Institutes, National Institutes of Health, Bethesda, MD, 20892, USA

    Haresh Mani

  4. Department of Anesthesiology, Clinical Center, National Institutes of Health, Bethesda, MD, 20892, USA

    Virginia Besch

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  1. Xizhong Cui
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  2. Junwu Su
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  3. Yan Li
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  4. Joseph Shiloach
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  5. Steven Solomon
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  7. Haresh Mani
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  8. Yvonne Fitz
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  9. Jia Weng
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  10. Laith Altaweel
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  11. Virginia Besch
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  12. Peter Q. Eichacker
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Correspondence to Peter Q. Eichacker.

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Cui, X., Su, J., Li, Y. et al. Bacillus anthracis cell wall produces injurious inflammation but paradoxically decreases the lethality of anthrax lethal toxin in a rat model. Intensive Care Med 36, 148–156 (2010). https://doi.org/10.1007/s00134-009-1643-9

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  • DOI: https://doi.org/10.1007/s00134-009-1643-9

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