Increased extra domain-A containing fibronectin and hepatic dysfunction during septic response: an in vivo and in vitro study.
A massive inflammatory reaction resulting from systemic cytokine release is the common pathway underlying sepsis or multiple organ dysfunction. The role of extra domain sequence A-containing fibronectin (EDA+FN) formation during the septic response is not known. The present study investigates the role of EDA+FN during the septic response under in vitro and in vivo conditions. The direct effects of interleukin-1, interleukin-6, and tumor necrosis factor-alpha on EDA+FN production were evaluated in primary cultured human hepatocytes and fibroblasts. Serial plasma EDA+FN levels were measured using an enzyme-linked immunosorbent assay in 24 patients who developed postoperative sepsis following general abdominal surgery of which there were 17 survivors and 7 non-survivors. EDA+FN secretion was significantly increased in cultured hepatocytes but not fibroblasts at 24 and 48 h following exposure to IL-1 compared to controls. In the clinical setting plasma EDA+FN levels in non-survivors were significantly higher than in survivors. Moreover, the EDA+FN levels were correlated closely with liver function tests. EDA+FN levels may represent a specific marker of vascular injury or systemic inflammatory response syndrome that is associated with an adverse clinical outcome.
Satoi
S
S
First Department of Surgery, Kansai Medical University, Moriguchi, Osaka, Japan.
Kitade
H
H
Hiramatsu
Y
Y
Kwon
A H
AH
Takahashi
H
H
Sekiguchi
K
K
Uehara
M
M
Oda
M
M
Yanagimoto
Y
Y
Miyashita
K
K
Sakashita
E
E
Kamiyama
Y
Y
D018806:APACHE; D000005:Abdomen / Q000601:surgery; D000368:Aged; D015415:Biomarkers; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000378:metabolism / Q000401:mortality; D011183:Postoperative Complications / Q000378:metabolism* / Q000401:mortality; D020033:Protein Isoforms / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D018746:Systemic Inflammatory Response Syndrome / Q000378:metabolism* / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015415:Biomarkers; D005353:Fibronectins; D007375:Interleukin-1; D015850:Interleukin-6; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha