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Infect. Immun., Jun 1996, 2167-2171, Vol 64, No. 6
AK May, RG Sawyer, T Gleason, A Whitworth and TL Pruett
Alpha-hemolysin is an Escherichia coli exotoxin that enhances bacterial
virulence, has profound effects on leukocytes in vitro, and induces the
release of interleukin-1 (IL-1) but not tumor necrosis factor (TNF) from
human monocytes in vitro. The purpose of this study was to examine
alpha-hemolysin's influence on virulence and TNF and IL-1 production in
vivo. Two genetically engineered, isogeneic strains of E. coli were used;
one variant produces alpha-hemolysin, and the other does not. Male BALB/c
mice were injected with either of the two variants and serum TNF and IL-1
were assayed. These results were compared with those obtained from the
injection of either of two serotypes of lipopolysaccharide (LPS). The
nonhemolytic E. coli strain produced no mortality and no significant
elevation of serum TNF or IL-1 levels. In contrast, equal inocula of the
hemolytic E. coli strain produced significant mortality and elevation of
serum IL-1 levels. No significant elevation of TNF levels was detected in
this group despite high-level mortality. A pattern of induction of
mortality and elevation of serum IL-1 levels without elevation of serum TNF
levels is distinct from the pattern typical of LPS. In these experiments,
both serotypes of LPS caused elevations of TNF and IL-1 levels whether or
not mortality was induced. Thus, alpha-hemolysin produces a cytokine
response in vivo that is similar to that previously demonstrated in vitro
by Bhakdi et al. (S. Bhakdi, M. Muhly, S. Korom, and G. Schmidt, J. Clin.
Invest. 85:1746-1753, 1990) and appears to induce mortality independently
of serum TNF.
Copyright © 1996, American Society for Microbiology
In vivo cytokine response to Escherichia coli alpha-hemolysin determined with genetically engineered hemolytic and nonhemolytic E. coli variants
Department of Surgery, Surgical Infectious Disease Laboratory, University of Virginia, Charlottesville 22908, USA.
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