scholarly journals Synergy between tumor necrosis factor and bacterial products causes hemorrhagic necrosis and lethal shock in normal mice.

1988 ◽  
Vol 85 (2) ◽  
pp. 607-611 ◽  
Author(s):  
J. L. Rothstein ◽  
H. Schreiber
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Hemorrhagic Necrosis ◽  
Lethal Shock ◽  
Necrosis Factor ◽  
Bacterial Products

scholarly journals Nonhematopoietic cells selected for resistance to tumor necrosis factor produce tumor necrosis factor.

1986 ◽  
Vol 164 (4) ◽  
pp. 1350-1355 ◽  
Author(s):  
B Y Rubin ◽  
S L Anderson ◽  
S A Sullivan ◽  
B D Williamson ◽  
E A Carswell ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cytotoxic Action ◽  
Surface Receptors ◽  
L Cells ◽  
Produce Tumor Necrosis Factor ◽  
Hemorrhagic Necrosis ◽  
Resistant Lines ◽  
Mouse Sarcoma ◽  
Necrosis Factor

TNF-resistant lines of L cells can be derived from TNF-sensitive populations by repeated exposure to TNF, and these resistant L cells, in contrast to sensitive L cells and other types of cells, lack demonstrable cell surface receptors for TNF. We have now found that TNF-resistant L cells produce a factor that is cytotoxic for L cells and has the following distinguishing characteristics of mouse TNF: it is a protein of 43 kD, composed of 16 kD subunits, that competes with TNF for receptor binding, induces hemorrhagic necrosis of the TNF-sensitive mouse sarcoma Meth A, has synergistic cytotoxic action with interferon, and its activity is neutralized by antibody to TNF. The two conclusions of this study are that cells selected for TNF resistance spontaneously produce a molecule resembling macrophage TNF, and that cells of nonhematopoietic origin are capable of producing TNF.

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.

scholarly journals The immunological basis of endotoxin-induced tumor regression. Requirement for a pre-existing state of concomitant anti-tumor immunity.

1978 ◽  
Vol 148 (6) ◽  
pp. 1560-1569 ◽  
Author(s):  
M J Berendt ◽  
R J North ◽  
D P Kirstein
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Immunity ◽  
Tumor Necrosis ◽  
Temporal Relationship ◽  
Tumor Regression ◽  
Effector T Cells ◽  
Hemorrhagic Necrosis ◽  
Concomitant Immunity ◽  
Necrosis Factor

It was shown that of four syngeneic, murine tumors investigated, only those that evoked the generation of a state of concomitant anti-tumor immunity were susceptible to endotoxin-induced regression. Moreover, the temporal relationship between the generation of concomitant immunity and the onset of susceptibility to endotoxin-induced regression points to the likely possibility that tumor regression depends on the preceding acquisition of the specifically-sensitized, effector T cells that express concomitant immunity. It is suggested that endotoxin-induced hemorrhagic necrosis which invariably precedes tumor regression serves to create conditions inside the tumor that are conducive to the entry and the functioning of effector T cells. It is also suggested that tumor necrosis factor causes hemorrhagic necrosis rather than tumor regression.

scholarly journals Glucocorticoid-mediated inhibition of endotoxin-induced intratumor tumor necrosis factor production and tumor hemorrhagic necrosis and regression.

1989 ◽  
Vol 170 (3) ◽  
pp. 703-710 ◽  
Author(s):  
R J North ◽  
E A Havell
Keyword(s):  
Tumor Necrosis Factor ◽  
Intravenous Injection ◽  
Subcutaneous Injection ◽  
Tumor Necrosis ◽  
Complete Regression ◽  
Tumor Necrosis Factor Production ◽  
The Core ◽  
Hemorrhagic Necrosis ◽  
Extensive Necrosis ◽  
Necrosis Factor

Intravenous injection of 25 micrograms of bacterial endotoxin on day 9 of growth of the SA1 sarcoma results in extensive necrosis of the core of this tumor and in its subsequent complete regression. Tumor hemorrhagic necrosis and regression failed to occur in mice that were given a subcutaneous injection of cortisone acetate or dexamethasone 12 h before being giving endotoxin. Inhibition of tumor hemorrhagic necrosis and regression by glucocorticoids was associated with inhibition of endotoxin-induced intratumor TNF production that normally takes place several h after endotoxin is given. In contrast, glucocorticoids had no effect on the ability of intravenously injected rTNF to cause tumor hemorrhagic necrosis and regression. The results lend further support to the belief that TNF is the predominant mediator of endotoxin-induced hemorrhagic necrosis of established murine tumors, and that hemorrhagic necrosis is a prerequisite for the immunologically mediated regression that follows.

scholarly journals The antitumor function of tumor necrosis factor (TNF), I. Therapeutic action of TNF against an established murine sarcoma is indirect, immunologically dependent, and limited by severe toxicity.

1988 ◽  
Vol 167 (3) ◽  
pp. 1067-1085 ◽  
Author(s):  
E A Havell ◽  
W Fiers ◽  
R J North
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Cells ◽  
Tumor Necrosis ◽  
Tumor Regression ◽  
Cytotoxic Action ◽  
Complete Regression ◽  
Severe Toxicity ◽  
Hemorrhagic Necrosis ◽  
Necrosis Factor

The ability of murine recombinant tumor necrosis factor (rTNF) and natural TNF in tumor-necrotizing serum (TNS) to cause regression of the SA1 sarcoma was investigated. We found that to cause regression of a 9-d SA1 sarcoma, near lethal quantities of rTNF and TNS had to be given to the host. However, even at these highly toxic doses, rTNF was not reliable at causing complete tumor regression. On the other hand, both types of TNF were reliable at causing a tumor hemorrhagic reaction that resulted in the destruction of greater than 75% of the tumor's center in 24 h. The TNF-induced hemorrhagic reaction involved the development of numerous petechial hemorrhages in the tumor's vascular bed, which apparently resulted from destruction of the tumor's blood vessels. It was possible to follow the development of the hemorrhagic reaction against time after giving rTNF or TNS by measuring the intratumor extravasation of 51Cr-labeled syngeneic red cells. According to this method, TNF-induced intratumor hemorrhaging was in progress within 1 h of giving TNF and continued for about a 6-h period. However, the hemorrhagic reaction was greatly reduced and complete regression of the rim of the living tumor tissue that survived hemorrhagic necrosis failed to occur, if SA1 sarcoma was growing in T cell-deficient (TXB) mice. This indicates that the TNF-induced hemorrhagic reaction is partly dependent, and the tumor regression that follows is completely dependent on host immunocompetence. This suggests in turn, that rTNF does not directly destroy SA1 tumor cells in vivo, even though it was shown that it can destroy SA1 tumor cells in vitro. This interpretation is supported by the additional findings that rTNF was no more therapeutic against a 3-d (3-mm) SA1 than against a 9-d (8-mm) SA1, and was no more therapeutic when injected directly into the tumor than when injected intravenously. Lastly it was possible to completely inhibit the ability of rTNF and TNS to cause tumor hemorrhagic necrosis and regression by infusing the host with a monospecific, polyvalent anti-rTNF antibody that neutralized the cytotoxic action of rTNF in vitro.

scholarly journals Type I interferon drives tumor necrosis factor–induced lethal shock

2009 ◽  
Vol 206 (9) ◽  
pp. 1873-1882 ◽  
Author(s):  
Liesbeth Huys ◽  
Filip Van Hauwermeiren ◽  
Lien Dejager ◽  
Eline Dejonckheere ◽  
Stefan Lienenklaus ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Inflammatory Diseases ◽  
White Blood Cells ◽  
Type I Interferons ◽  
Type I ◽  
Antitumor Effects ◽  
Type I Ifns ◽  
Lethal Shock ◽  
Necrosis Factor

Tumor necrosis factor (TNF) is reputed to have very powerful antitumor effects, but it is also a strong proinflammatory cytokine. Injection of TNF in humans and mice leads to a systemic inflammatory response syndrome with major effects on liver and bowels. TNF is also a central mediator in several inflammatory diseases. We report that type I interferons (IFNs) are essential mediators of the lethal response to TNF. Mice deficient in the IFN-α receptor 1 (IFNAR-1) or in IFN-β are remarkably resistant to TNF-induced hypothermia and death. After TNF injection, IFNAR-1−/− mice produced less IL-6, had less bowel damage, and had less apoptosis of enterocytes and hepatocytes compared with wild-type (WT) mice. Extensive gene expression analysis in livers of WT and IFNAR-1−/− mice revealed a large deficiency in the response to TNF in the knockout mice, especially of IFN-stimulated response element–dependent genes, many of which encode chemokines. In livers of IFNAR-1−/− mice, fewer infiltrating white blood cells (WBCs) were detected by immunohistochemistry. Deficiency of type I IFN signaling provided sufficient protection for potentially safer therapeutic use of TNF in tumor-bearing mice. Our data illustrate that type I IFNs act as essential mediators in TNF-induced lethal inflammatory shock, possibly by enhancing cell death and inducing chemokines and WBC infiltration in tissues.

scholarly journals Uncovering the dark side of TNF

2007 ◽  
Vol 204 (9) ◽  
pp. 2013-2013 ◽  
Author(s):  
Hema Bashyam
Keyword(s):  
Weight Loss ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Antitumor Agent ◽  
Dark Side ◽  
Lethal Shock ◽  
Necrosis Factor ◽  
Potential Antitumor

In the early 1980s, in search of the cytokine that triggers disease- associated weight loss and lethal shock, Anthony Cerami and Bruce Beutler purified “cachectin.” They soon found out that their malevolent cytokine already had another name—tumor necrosis factor (TNF)—and was being lauded as a potential antitumor agent.

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