Hepatic Acute Phase Protein Synthesis is Indirectly Regulated by Tumor Necrosis Factor

1990 ◽  
Vol 30 (10) ◽  
pp. 1181-1188 ◽  
Author(s):  
PAUL E. BANKEY ◽  
JOHN E. MAZUSKI ◽  
MARIAESTELA ORTIZ ◽  
JOSE M. FULCO ◽  
FRANK B. CERRA
Keyword(s):  
Protein Synthesis ◽  
Tumor Necrosis Factor ◽  
Acute Phase ◽  
Tumor Necrosis ◽  
Acute Phase Protein ◽  
Phase Protein ◽  
Necrosis Factor

Circulating interleukin 1 and tumor necrosis factor during inflammation

1987 ◽  
Vol 253 (6) ◽  
pp. R922-R928 ◽  
Author(s):  
L. L. Moldawer ◽  
J. Gelin ◽  
T. Schersten ◽  
K. G. Lundholm
Keyword(s):  
Tumor Necrosis Factor ◽  
Acute Phase ◽  
Tumor Necrosis ◽  
Acute Phase Protein ◽  
Interleukin 1 ◽  
Sterile Inflammation ◽  
Acute Phase Protein Response ◽  
Phase Protein ◽  
Protein Response ◽  
Necrosis Factor

It is proposed that interleukin 1 (IL 1) and tumor necrosis factor (TNF) alpha play central roles in the host's response to inflammation. Yet circulating concentrations have not been frequently measured in many inflammatory states. Serum levels of IL 1 and TNF were evaluated in mice with a tumor, sterile inflammation, endotoxinemia, or generalized peritonitis where an acute-phase protein response was documented. In tumor-bearing mice, no IL 1 or TNF could be detected despite marked increases in the serum concentration of the acute-phase reactant protein, amyloid P. In mice with peritonitis, induced by cecal ligation and perforation, or a turpentine-induced subcutaneous abscess, IL 1 but not TNF could be detected in the serum. Only expansion of the reticuloendothelial system with Corynebacterium parvum and subsequent challenge with endotoxin resulted in serum TNF appearance. The failure to observe IL 1 or TNF in any of the disorders could not be explained by inhibitors. Rather, the data suggest that a hepatic acute-phase protein response can occur during inflammatory states without the appearance of either IL 1 or TNF in the circulation. Circulating levels of both monokines do not appear to be a universal finding in inflammation.

Pentoxifylline decreases body weight loss and muscle protein wasting characteristics of sepsis

1993 ◽  
Vol 265 (4) ◽  
pp. E660-E666 ◽  
Author(s):  
D. Breuille ◽  
M. C. Farge ◽  
F. Rose ◽  
M. Arnal ◽  
D. Attaix ◽  
...  
Keyword(s):  
Body Weight ◽  
Protein Synthesis ◽  
Acute Phase ◽  
Protein Metabolism ◽  
Muscle Wasting ◽  
Acute Phase Protein ◽  
Muscle Protein ◽  
Liver Protein ◽  
Phase Protein

Sepsis induces metabolic disorders that include loss of body weight, muscle wasting, and acute-phase protein synthesis in liver. Cytokines are generally recognized as active mediators of these disorders, and the implication of tumor necrosis factor (TNF) has been frequently discussed in the recent past. However, the identity of the active agent in alterations of protein metabolism is still controversial. To improve our understanding of the role of cytokines in mediating muscle wasting observed in sepsis, we investigated muscle and liver protein metabolism in the following three groups of rats: infected control rats (INF-C); infected rats pretreated with pentoxifylline (PTX-INF), which is a potent inhibitor of TNF secretion; and pair-fed rats for the PTX-INF group pretreated with pentoxifylline. Pentoxifylline nearly completely suppressed TNF secretion but did not influence the transient fall in rectal temperature, the decreased hematocrit, and the increased liver protein mass and synthesis observed in INF-C rats. Pentoxifylline decreased the anorexia, the loss of body weight and muscle protein observed in INF-C animals, and partially prevented the decrease in muscle protein synthesis induced by infection. The overall data indicate that pentoxifylline is an effective agent in mitigating the characteristic muscle protein wasting induced by sepsis and confirm the limited role of TNF in the mediation of the acute-phase protein synthesis. Our results suggest a probable implication of TNF in the regulation of protein balance in muscle but do not allow discarding possible implication of other mediators that would be inhibited by pentoxifylline.

Enhancement of tumor necrosis factor-induced endothelial cell injury by cycloheximide

1990 ◽  
Vol 259 (2) ◽  
pp. L123-L129
Author(s):  
K. B. Nolop ◽  
U. S. Ryan
Keyword(s):  
Endothelial Cells ◽  
Protein Synthesis ◽  
Endothelial Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Morphological Evidence ◽  
Human Aorta ◽  
Dependent Manner ◽  
Inhibitor Of Protein Synthesis ◽  
Necrosis Factor

Tumor necrosis factor (TNF), a potent polypeptide mediator released by activated monocytes and macrophages, has a number of proinflammatory effects on endothelial cells. TNF is cytotoxic to tumor cells in vivo and in vitro, but TNF-induced toxicity to endothelial cells is less well established. We now report that cycloheximide (CHX), an inhibitor of protein synthesis, renders endothelial cells highly susceptible to TNF-induced lysis. TNF alone did not change the overall rate of protein synthesis by endothelial cells, whereas the addition of CHX completely abolished protein synthesis. Endothelial cells incubated in TNF alone in high concentrations (up to 1,000 U/ml) showed minimal rounding up and release of 51Cr. Likewise, CHX alone (5 micrograms/ml) had no significant effect on endothelial cell morphology and release of 51Cr. However, incubation of endothelial cells in both CHX and TNF caused injury in a dose-dependent manner. Morphological evidence of cell retraction, rounding, and detachment began within 2 h, but specific 51Cr release did not begin to rise until after 4 h. These changes were not observed when endothelial cells were incubated with TNF/CHX at 4 degrees C. The combination of TNF/CHX was lethal to all endothelial cells tested (bovine pulmonary artery, human umbilical vein, and human aorta), with human aortic cells showing the most pronounced changes. We conclude that healthy endothelial cells are resistant to TNF-induced lysis, but inhibition of their ability to make protein renders them highly susceptible.

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.

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