Molecular analysis of sepsis induced changes in the liver: microarray study in a porcine model of acute fecal peritonitis with fluidresuscitation

Sepsis and septic shock are frequently encountered in the intensive care unit. Despite the evolution of intensive care medicine over the last decades, septic shock is still associated with a high mortality and the complications of sepsis such as cholestasis, liver dysfunction and massive intravascular volume deficit.Little is known about the whole pattern of changes at the ranscriptional level during development of acute sepsis. Here we present the a detailed molecular biological analysis of the events in the liver during the first day of acute bacterial infection in a clinically-relevant model of porcine peritoneal sepsis.Before and 21 hours after induction of sepsis by autologous fecal inoculum liver samples were taken for microarray analysis. There were two groups of animals (7 control and 8 sepsis), 2 of each group where used in microarray, the remaining were used for confirmation of selected genes by RT-PCR. Pathway analysis revealed that in acute sepsis gene expression was significantly changed in processes related to apoptosis, inflammation and oxidant/redox balance. Although after 21 hours these animals are expected to die within the next 3 to 4 hours from massive complications, functional induction of apoptosis could not be confirmed.Computer analysis identified 3 key regulators genes (IL8, CCL2 and CXCL2) among the first genes to be upregulated specifically in the sepsis group and that can directly or indirectly control the bulk of the sepsis response. Induction of inflammatory mediators by sepsis was supported by the detection of corresponding cytokines (IL-6 and IL-8) in the blood.status: publishe