Molecular characterization of the acute inflammatory response to infections with gram-negative versus gram-positive bacteria.
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.
D016207:Cytokines / Q000097:blood* / Q000235:genetics*; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D016905:Gram-Negative Bacterial Infections / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D016908:Gram-Positive Bacterial Infections / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood; D007962:Leukocytes / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology
D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides