The septic abscess wall: a cytokine-generating organ associated with portal venous cytokinemia, hepatic outflow fibrosis, XXXX , inflammatory cell sequestration, hepatocellular lipid deposition, and focal cell death.

@entity2868 @entity295 @entity82 @entity568 @entity6177 @entity1505 @entity3426 @entity5501 @entity35 @entity526
An acute septic inflammatory response with access to the portal circulation was created in a @entity35 model using an @entity6177 composed of a sterile agar pellet, or one contaminated with 102 @entity526 (E. coli) and 109 Bacteriodes fragilis ( @entity2868 ). After 3 days postimplantation, a well-formed @entity6177 occurred whose wall showed @entity568 DNA by PCR and @entity568 mRNA by in situ hybridization. Portal venous blood draining into the liver from the @entity6177 had increased levels of @entity1505 , @entity3426 , and @entity568 in both sterile and septic groups compared with a control normal animal group. Increased levels of these cytokines were also found in suprahepatic inferior vena caval blood, but were correlated with the higher portal vein levels, suggesting a gradient from abscess wall to portal vein into the systemic circulation via the liver. Liver histology demonstrated @entity5501 centering on the central vein, growing worse with progression from normal in control, to sterile, to septic. Similarly, the degree of intrahepatic myeloperoxidase-positive inflammatory cell infiltration and hepatocellular lipid deposition and apoptosis also increased from control, to sterile, to septic. Gene expression by in situ hybridization demonstrated a significant increase in @entity568 and fibrinogen mRNAs in cells surrounding the central vein in sterile and septic animals, being greatest in animals with @entity295 , associated with an increased deposition of collagen in the central vein area, most prominent in the septic liver. The pericentral vein cells with @entity568 and fibrinogen mRNA increases paralleled the increases in cells containing @entity568 and fibrinogen mRNAs in the abscess walls of sterile and septic animals, respectively. The data suggest that an @entity6177 , especially when contaminated with gram-negative bacteria, induces mRNA-generated cytokine responses in the abscess wall that are related to increased portal venous levels of the inflammatory cytokines @entity1505 , @entity3426 , and @entity568 perfusing the liver. These, in turn, induce localized production of @entity568 and fibrinogen mRNAs in cells at the central vein area with resultant outflow @entity82 and increased inflammatory cell sequestration within the liver lobular sinuses. This is associated with a generalized inflammatory response and intrahepatic portal sinusoid congestion. There is also increased hepatocellular lipid deposition and apoptosis. Thus, the cytokine production of the abscess wall itself appears to be a major mediator of the septic hepatic response.
