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