Molekulare Charakterisierung der akuten Immunantwort von Gram positiver und Gram negativer Sepsis

Abstract

In the present study, we examine the diversity in host response to Gram negative and Gram positive pathogens by focusing on the differential proinflammatory cytokine responses in the plasma of septic patients. Moreover, a genome-wide survey of gene expression pattern was performed on whole blood from human volunteers stimulated ex vivo with Gram negative and Gram positive microbial products. Blood plasma was obtained from 52 patients with Gram negative or Gram positive sepsis on admission and evaluated for proinflammatory cytokine concentrations. In addition, whole blood from healthy human volunteers was stimulated ex vivo with E. coli lipopolysaccharide (LPS) or heat-killed Staphylococcus aureus (SAC). Gene expression pattern were also obtained from ex vivo stimulated whole blood leukocytes using GeneChip technology. Plasma concentrations of TNF-α, IL-1 Ra, IL-8, IL-10, IL-18BP, procalcitonin, and protein C did not differ between patients with Gram negative and Gram positive sepsis. However, plasma IL-1ß and IL-18 concentrations were significantly higher in patients with Gram positive sepsis. Ex vivo stimulation of whole blood with SAC markedly increased IL-1ß and IL-18 compared to LPS stimulation. GeneChip technology supervised analysis revealed 758 cross-validated probe sets (genes) that are capable of accurately discriminating among Gram negative-stimulated, Gram positive-stimulated, and unstimulated whole blood leukocytes. Furthermore, of these 758 genes, only 87 were upregulated in both conditions greater than 2-fold and only 43 genes were commonly down- regulated. Although the physiological response of the host to Gram negative and Gram positive sepsis may appear similar, the early inflammatory and immunological response to these pathogens seems to significantly differ depending upon the inciting organism.