当前位置： SCI文献检索 > CRITICAL CARE MEDICINE期刊下所有文献 > Acute-phase gene expression correlates with intrahepatic tumor necrosis factor-alpha abundance but not with plasma tumor necrosis factor concentrations during sepsis/systemic inflammatory response syndrome in the rat.

Acute-phase gene expression correlates with intrahepatic tumor necrosis factor-alpha abundance but not with plasma tumor necrosis factor concentrations during sepsis/systemic inflammatory response syndrome in the rat.

Abstract：

OBJECTIVES:To test the hypothesis that after cecal ligation and puncture in the rat, there is increased expression of the tumor necrosis factor (TNF)/interleukin-1-dependent, acute-phase reactant alpha 1-acid glycoprotein in the liver, and that this change correlates temporally with increased abundance of TNF-alpha in the hepatic parenchyma but not with circulating concentrations of TNF-alpha. DESIGN:Prospective, randomized, controlled study. SETTING:Research laboratory at the University of Pennsylvania School of Medicine. SUBJECTS:Male, adolescent Sprague-Dawley rats, weighing 200 to 300 g. INTERVENTIONS:The procedure of cecal ligation and single puncture with an 18-gauge needle was performed in one group of animals. Control animals underwent sham operation. At 0, 3, 6, 16, 24, 48, and 72 hrs after either procedure, blood was collected and the liver was isolated and perfusion-fixed with 2% paraformaldehyde. In a second group of animals, liver tissue was harvested for isolation of total hepatic RNA. MEASUREMENTS AND MAIN RESULTS:Northern blot hybridization analysis demonstrated an increase in steady-state concentrations of alpha 1-acid glycoprotein messenger RNA that peaked at 16 hrs after cecal ligation and puncture. The alpha 1-acid glycoprotein messenger RNA was not detected in control animals. TNF-alpha concentrations in the plasma, as determined by enzyme-linked immunosorbent assay, were detected 3 and 6 hrs after cecal ligation and puncture. However, TNF-alpha concentrations were undetectable in the plasma at other time points after cecal ligation and puncture and at all time points in the sham-operated animals. Immunohistochemical staining of 7-micron hepatic sections demonstrated a progressive increase in TNF-alpha abundance, with a peak at 16 hrs. Alterations in alpha 1-acid glycoprotein gene expression correlated in time with intrahepatic TNF-alpha abundance, but not with plasma TNF-alpha concentrations. CONCLUSIONS:The changes in TNF-alpha-dependent hepatic gene expression that accompany an animal model of the systemic inflammatory response syndrome correlate with intrahepatic, and not circulating, TNF-alpha concentrations and reflect paracrine, and not endocrine, activity. Therefore, plasma concentrations of TNF-alpha do not appropriately reflect hepatocellular responses during the systemic inflammatory response syndrome.

journal_name

Crit Care Med

journal_title

Critical care medicine

authors

Andrejko KM,Deutschman CS

doi

10.1097/00003246-199612000-00004

subject

Has Abstract

pub_date

1996-12-01 00:00:00

pages

1947-52

issue

eissn

0090-3493

issn

1530-0293

journal_volume

pub_type

杂志文章

在线工具

Acute-phase gene expression correlates with intrahepatic tumor necrosis factor-alpha abundance but not with plasma tumor necrosis factor concentrations during sepsis/systemic inflammatory response syndrome in the rat.