Systemic cytokine response in murine anthrax.
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.
Popov
Serguei G
SG
Advanced Biosystems Inc, Manassas, VA 20110, USA. serguei.popov@analex.com
Popova
Taissia G
TG
Grene
Edith
E
Klotz
Francis
F
Cardwell
Jennifer
J
Bradburne
Chris
C
Jama
Yusuf
Y
Maland
Matthew
M
Wells
Jay
J
Nalca
Aysegul
A
Voss
Tom
T
Bailey
Charles
C
Alibek
Ken
K
D000818:Animals; D000881:Anthrax / Q000276:immunology*; D001408:Bacillus anthracis; D016207:Cytokines / Q000032:analysis / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains
D016207:Cytokines