Lethality during continuous anthrax lethal toxin infusion is associated with circulatory shock but not inflammatory cytokine or nitric oxide release in rats

• DOI: 10.1152/ajpregu.00593.2003
• Publication Date: 2004-03-05T21:03:06Z
• Authors: Xizhong Cui; Mahtab Moayeri; Yan Li; Xuemei Li; Michael Haley; Yvonne Fitz; Rosaly Correa-Araujo; Steven M. Banks; Stephen H. Leppla; Peter Q. Eichacker
• Keywords: Lethality

Although circulatory shock related to lethal toxin (LeTx) may play a primary role in lethality due Bacillus anthracis infection, its mechanisms are unclear. We investigated whether LeTx-induced is associated with inflammatory cytokine and nitric oxide (NO) release. Sprague-Dawley rats central venous arterial catheters received 24-h infusions of LeTx (lethal factor 100 microg/kg; protective antigen 200 microg/kg) that produced death beginning at 9 h 7-day mortality rate 53%. By h, mean blood pressure, heart rate, pH, base excess were decreased lactate hemoglobin levels increased nonsurvivors compared survivors controls (diluent only) (P < or = 0.05 for each comparing the 3 groups). Despite these changes, oxygen circulating leukocytes platelets not TNF-alpha, IL-beta, IL-6, IL-10 either controls. Nitrate/nitrite tissue histology also did differ animals In additional experiments, although Escherichia coli LPS similar rates (54 56%, respectively) times (13.2 +/- 0.8 vs. 11.0 1.7 controls, only reduced leukocytes, platelets, IL-2 IL-1 alpha -1 beta, IL-10, interferon-gamma, granulocyte macrophage-colony stimulating factor, RANTES, migratory inhibitory protein-1 alpha, -2, -3, monocyte chemotactic protein-1, as well nitrate/nitrite (all P effects LPS). Thus, contrast LPS, excessive NO release does appear contribute occurring this model. therapies modulate host mediators be applicable fo caused by other bacterial toxins, they LeTx.