Kinetics of endotoxin-induced acute-phase protein gene expression and its modulation by TNF-alpha monoclonal antibody.
The kinetics of cytokine release and acute-phase protein gene expression in liver were investigated in rats receiving a single intraperitoneal bolus dose of Escherichia coli lipopolysaccharide (LPS). Transient elevation of plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were detected. Hepatic messenger RNAs for two acute-phase proteins, alpha 1-acid glycoprotein and alpha 2-macroglobulin, were measured by Northern blotting and were found to increase to a maximum at 24 h, returning to normal by 72 h; plasma concentrations showed a slower but more sustained rise. For albumin, hepatic mRNA was reduced, being minimum at 24 h with a similar but more prolonged fall in plasma concentration. Pretreatment of rats with TNF-alpha monoclonal antibody 4 h before LPS ameliorated weight loss and anorexia, partially suppressed the rise in IL-6 and reduced the increase in hepatic mRNA and plasma concentrations of alpha 1-acid glycoprotein and alpha 2-macroglobulin. For albumin, however, such pretreatment had no effect on the fall in either hepatic mRNA or plasma concentration. Thus we have defined an in vivo role of TNF-alpha in the control of endotoxin-induced acute-phase protein generation.
Sharma
R J
RJ
Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, London, United Kingdom.
Macallan
D C
DC
Sedgwick
P
P
Remick
D G
DG
Griffin
G E
GE
D000209:Acute-Phase Proteins / Q000235:genetics*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D015870:Gene Expression; D015850:Interleukin-6 / Q000097:blood; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D000511:alpha-Macroglobulins / Q000032:analysis
D000209:Acute-Phase Proteins; D000911:Antibodies, Monoclonal; D004731:Endotoxins; D015850:Interleukin-6; D012333:RNA, Messenger; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D000511:alpha-Macroglobulins