INHIBITION OF TUMOR NECROSIS FACTOR-INDUCED LIVER TOXICITY AND LETHALITY BY THE ACUTE PHASE PROTEINS α-1-ACID GLYCOPROTEIN AND α-1-ANTITRYPSIN.

Shock ◽  
1997 ◽  
Vol 7 (Supplement) ◽  
pp. 65
Author(s):  
C. Libert ◽  
W. Van Molle ◽  
T. Hochepied ◽  
P. Ameloot ◽  
B. Everaerdt ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Acute Phase ◽  
Tumor Necrosis ◽  
Liver Toxicity ◽  
Acute Phase Proteins ◽  
Acid Glycoprotein ◽  
Necrosis Factor

Hormonal and metabolic response to recombinant human tumor necrosis factor in rat: in vitro and in vivo

1988 ◽  
Vol 255 (2) ◽  
pp. E206-E212
Author(s):  
R. S. Warren ◽  
H. F. Starnes ◽  
N. Alcock ◽  
S. Calvano ◽  
M. F. Brennan
Keyword(s):  
Tumor Necrosis Factor ◽  
Trace Metal ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Tumor Necrosis ◽  
Metabolic Response ◽  
Zinc Transport ◽  
Necrosis Factor

Tumor necrosis factor (TNF; cachectin) has been implicated as a mediator of the toxic manifestations of overwhelming bacterial infection as well as the chronic catabolic state of cancer cachexia. We have examined the acute metabolic and hormonal response after administration of recombinant human TNF in the rat. TNF given by intraperitoneal injection produced dose- and time-related increases in hepatic amino acid uptake, decreases in serum trace metal concentrations, and a pattern of endocrine hormone alterations characteristic of the acute phase response to tissue injury. In vitro zinc transport studies by rat hepatocytes cultured in the presence of TNF alone, or in combination with recombinant human interleukin 1, another mediator of the acute phase response, demonstrated that neither monokine was capable of directly stimulating zinc transport into cells. These findings suggest that TNF may function as an endogenous mediator of the early metabolic response to sepsis and that the trace metal changes induced by TNF in vivo may occur through a secondary mechanism.

scholarly journals Tumor Necrosis Factor Receptor p55-Deficient Mice Respond to Acute Yersinia enterocolitica Infection with Less Apoptosis and More Effective Host Resistance

2000 ◽  
Vol 68 (3) ◽  
pp. 1243-1251 ◽  
Author(s):  
Yi-Xue Zhao ◽  
Ginette Lajoie ◽  
Hongwei Zhang ◽  
Basil Chiu ◽  
Ursula Payne ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Necrosis Factor ◽  
Yersinia Enterocolitica ◽  
Acute Phase ◽  
Host Defense ◽  
Bacterial Infections ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Interleukin 10 ◽  
Necrosis Factor

ABSTRACT Tumor necrosis factor (TNF) has generally been regarded as a protective cytokine in host defense against bacterial infections. In the present study, we evaluated the role of TNF in the acute phase of infection by Yersinia enterocolitica by using mice rendered genetically deficient in TNF receptor p55 (TNFRp55−/−). Unexpectedly, TNFRp55−/− mice showed more effective resistance to the bacteria, reflected in enhanced bacterial clearance and less tissue damage, than did control C57BL/6 mice. C57BL/6 mice showed evidence of extensive apoptosis in the spleen accompanied by a selective decrease in the CD4+-T-cell population of splenocytes, whereas TNFRp55−/− mice were spared these changes. The splenocytes from TNFRp55−/− mice also maintained a robust gamma interferon IFN-γ response to mitogenic stimulation, while the comparable response in C57BL/6 mice was impaired. In addition, splenocytes harvested from infected mice demonstrated lower production of interleukin-10 IL-10 in TNFRp55−/− mice than in C57BL/6 mice. These findings suggest that Yersinia can induce TNFRp55-mediated apoptosis of splenocytes in the acute phase of the infection and that alteration of T-cell-generated cytokines can dramatically alter the early events in host defense against this pathogen.

scholarly journals Protection by alpha 1-acid glycoprotein against tumor necrosis factor-induced lethality.

1994 ◽  
Vol 180 (4) ◽  
pp. 1571-1575 ◽  
Author(s):  
C Libert ◽  
P Brouckaert ◽  
W Fiers
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Acute Phase Protein ◽  
Clotting Time ◽  
Protective Capacity ◽  
Lethal Challenge ◽  
Acid Glycoprotein ◽  
Liver Transaminases ◽  
Lethal Shock ◽  
Necrosis Factor

We here report that alpha 1-acid glycoprotein, a typical acute phase protein, protects mice from lethal shock induced by tumor necrosis factor (TNF) or endotoxin. The protection is observed both in normal and in galactosamine-sensitized mice. Optimal desensitization requires at least 3 mg alpha 1-acid glycoprotein administered 2 h before the lethal challenge. Under these conditions, complete inhibition of all TNF-induced metabolic changes was observed: fall in body temperature, release of liver transaminases, enhanced clotting time, and mortality. The known platelet aggregation-inhibitory activity of alpha 1-acid glycoprotein provides a possible explanation for this protective capacity.

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