Systemic cytokine response in murine anthrax.

Abstract

Systemic pro-inflammatory cytokine release has been previously implicated as a major death-causing factor in anthrax, however, direct data have been absent. We determined the levels of IL-1 beta, IL-6 and TNF-alpha in serum of mice challenged with virulent (Ames) or attenuated (Sterne) strains of Bacillus anthracis. More than 10-fold increase in the IL-1beta levels was detected in Ames-challenged Balb/c mice, in contrast to more susceptible C57BL/6 mice, which showed no IL-1beta response. Balb/c mice have also responded with higher levels of IL-6. The A/J mice demonstrated IL-1beta and IL-6 systemic response to either Ames or Sterne strain of B. anthracis, whereas no increase in TNF-alpha was detected in any murine strain. We used RT-PCR for gene expression analyses in the liver which often is a major source of cytokines and one of the main targets in infectious diseases. A/J mice challenged with B. anthracis (Sterne) showed increased gene expression for Fas, FasL, Bax, IL-1 beta, TNF-alpha, TGF-beta, MIP-1alpha, KC and RANTES. These data favour the hypothesis that apoptotic cell death during anthrax infection causes chemokine-induced transmigration of inflammatory cells to vitally important organs such as liver. Administration of caspase inhibitors z-VAD-fmk and ac-YVAD-cmk improved survival in Sterne-challenged mice indicating a pathogenic role of apoptosis in anthrax.

• Authors: Serguei G Popov, Taissia G Popova, Edith Grene, Francis Klotz, Jennifer Cardwell, Chris Bradburne, Yusuf Jama, Matthew Maland, Jay Wells, Aysegul Nalca, Tom Voss, Charles Bailey, Ken Alibek
• Journal: Cellular microbiology (Cell Microbiol) Vol. 6 Issue 3 Pg. 225-33 (Mar 2004) ISSN: 1462-5814 [Print] India
• PMID: 14764106 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cytokines

Topics

• Animals
• Anthrax (immunology)
• Bacillus anthracis
• Cytokines (analysis, immunology)
• Mice
• Mice, Inbred Strains