title: Molecular analysis of sepsis-induced changes in the liver: microarray study in a porcine model of acute fecal peritonitis with fluid resuscitation.
abstract: Sepsis and septic shock are frequently encountered in the intensive care unit. Despite the evolution of intensive care medicine during the last decades, septic shock is still associated with high mortality and complications of sepsis such as cholestasis, liver dysfunction, and massive intravascular volume deficit. Little is known about the whole pattern of changes at the transcriptional level during the development of acute sepsis. Here we present 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 h 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), two of each group where used in microarray, the remaining were used for confirmation of selected genes by real-time polymerase chain reaction. 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 h these animals are expected to die within the next 3 to 4 h from massive complications, functional induction of apoptosis could not be confirmed. Computer analysis identified three key regulator genes (IL8, CCL2, and CXCL2) among the first genes to be upregulated specifically in the sepsis group, and these 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 (interleukin 6 and interleukin 8) in the blood.
authors.affiliation: Liver Research Facility & Labo Hepatology, Faculty of Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Hannah
authors.initials: H
authors.lastname: van Malenstein
authors.forename: Joost
authors.initials: J
authors.lastname: Wauters
authors.forename: Dieter
authors.initials: D
authors.lastname: Mesotten
authors.forename: Lies
authors.initials: L
authors.lastname: Langouche
authors.forename: Rita
authors.initials: R
authors.lastname: De Vos
authors.forename: Alexander
authors.initials: A
authors.lastname: Wilmer
authors.forename: Jos
authors.initials: J
authors.lastname: van Pelt
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D005440:Fluid Therapy / Q000379:methods*; D016209:Interleukin-8 / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010538:Peritonitis / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D012151:Resuscitation; D018805:Sepsis / Q000503:physiopathology* / Q000628:therapy; D013552:Swine
chemical_list: D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D016209:Interleukin-8