Molecular characterization of the acute
septic response to Gram negative versus Gram positive bacterial
infections
Abstract:
Sepsis caused by gram-negative bacteria and that caused by
gram-positive bacteria often manifest similar clinical features. We
investigated plasma proinflammatory cytokine profiles in patients with
sepsis due to gram-positive and gram-negative bacteria and studied the
cytokine production and differential gene regulation of leukocytes
stimulated ex vivo with Escherichia coli lipopolysaccharide or
heat-killed Staphylococcus aureus. Concentrations of tumor necrosis
factor alpha, interleukin 1 receptor antagonist (IL-1Ra), IL-8, IL-10,
IL-18 binding protein, procalcitonin, and protein C in plasma did not
differ between patients with sepsis due to gram-negative and
gram-positive bacteria. However, plasma IL-1beta, IL-6, and IL-18
concentrations were significantly higher in patients with sepsis due
to gram-positive bacteria. Ex vivo stimulation of whole blood with
heat-killed S. aureus markedly increased IL-1beta and IL-18 levels
more than E. coli lipopolysaccharide stimulation. Microarray analysis
revealed at least 359 cross-validated probe sets (genes) significant
at the P < 0.001 level whose expression discriminated among
gram-negative-organism-stimulated, gram-positive-organism-stimulated,
and unstimulated whole-blood leukocytes. The host inflammatory
responses to gram-negative and gram-positive stimuli share some common
response elements but also exhibit distinct patterns of cytokine
appearance and leukocyte gene expression.
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