The septic abscess wall: a cytokine-generating organ associated with portal venous cytokinemia, hepatic outflow fibrosis, sinusoidal congestion, inflammatory cell sequestration, hepatocellular lipid deposition, and focal cell death.
An acute septic inflammatory response with access to the portal circulation was created in a rat model using an intra-abdominal abscess composed of a sterile agar pellet, or one contaminated with 102 Escherichia coli (E. coli) and 109 Bacteriodes fragilis (B. fragilis). After 3 days postimplantation, a well-formed intra-abdominal abscess occurred whose wall showed IL-6 DNA by PCR and IL-6 mRNA by in situ hybridization. Portal venous blood draining into the liver from the intra-abdominal abscess had increased levels of TNF-alpha, IL-1beta, and IL-6 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 sinusoidal congestion 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 IL-6 and fibrinogen mRNAs in cells surrounding the central vein in sterile and septic animals, being greatest in animals with sepsis, associated with an increased deposition of collagen in the central vein area, most prominent in the septic liver. The pericentral vein cells with IL-6 and fibrinogen mRNA increases paralleled the increases in cells containing IL-6 and fibrinogen mRNAs in the abscess walls of sterile and septic animals, respectively. The data suggest that an intra-abdominal abscess, 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 TNF-alpha, IL-1beta, and IL-6 perfusing the liver. These, in turn, induce localized production of IL-6 and fibrinogen mRNAs in cells at the central vein area with resultant outflow fibrosis 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.
Ceydeli
Adil
A
Department of Cell Biology, New Jersey Medical School/UMDNJ, 30 Bergen Street, Newark, NJ 07101, USA.
Condon
Michael R
MR
Siegel
John H
JH
D018784:Abdominal Abscess / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D016923:Cell Death; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis / Q000209:etiology / Q000473:pathology; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics; D050356:Lipid Metabolism; D008099:Liver / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D008107:Liver Diseases / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D009017:Morbidity; D011169:Portal Vein / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D013242:Sterilization; D015996:Survival Rate; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000503:physiopathology; D014682:Vena Cava, Inferior / Q000503:physiopathology
D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger