Detection of Tumour Necrosis Factor‐Like Cytotoxicity in Serum from Patients With Septicaemia but Not from Untreated Cancer Patients

Waage, Anders; Espevik, Terje; Lamvik, Jon

doi:10.1111/j.1365-3083.1986.tb02194.x

Cited by 122 publications

(32 citation statements)

References 10 publications

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“…The observations concerning the presence of TNF and IL-1 in the serum of cancer patients are inconsistent, however. Moldawer et al (1988) could not detect IL-1 and TNF bioactivities in the plasma of weight-losing cancer patients; other investigators have made similar observations (Scuderi et al, 1986;Waage et al, 1986;Selby et al, 1987;Socher et al, 1988b). By contrast, the presence of TNF has been observed in the serum of children with acute lymphoblastic leukaemia (Saarinen et al, 1990), in other cancer patients (Aderka et al, 1985;Balkwill et al, 1987), and in cachectic tumourbearing rats (Stovroff et al, 1989).…”

Section: Humoral Mediatorsmentioning

confidence: 82%

Humoral mediation for cachexia in tumour-bearing rats

Tessitore

Costelli²,

Baccino³

1993

Br J Cancer

109

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Summary Early and severe loss of body weight associated with pronounced tissue changes developed in rats transplanted with a fast-growing ascites hepatoma (Yoshida AH-130). The protein content showed an early and marked fall in the skeletal muscle, while in the liver it transiently increased 4 days after implantation then declined to values lower than in control animals. Protein loss in gastrocnemius muscle and liver resulted mainly from enhancement of protein catabolism (Tessitore L. et al., Biochem. J., 241: 153-158, 1987). In contrast to the tumour-bearing rats, in the pair-fed animals the initial body weight was maintained, while the protein mass decreased sharply in the liver and moderately in the grastrocnemius muscle. In host animals total plasma protein decreased during the period of tumour growth, while both triglycerides and total cholesterol markedly increased. Glucose remained unchanged even when overt cachexia had developed. The total free amino acid concentration in the plasma of tumour-bearing rats decreased slightly by day 4 and returned to values close to those of controls in the late stages of tumour growth. By contrast, in the pair-fed controls the plasma levels of triglycerides and particularly of total free amino acids and glucose decreased over the whole experimental period, whereas total protein and cholesterol were unchanged. Marked perturbations in the hormonal homeostasis developed early after tumour transplantation. The plasma levels of glucagon, corticosterone and catecholamines rose sharply, while those of insulin and thyroid hormones decreased. Furthermore, high plasma concentrations of prostaglandin E2 (PGE2) and tumour necrosis factor (TNF) were observed over the whole experimental period. IL-I-like activity, TNF and PGE2 were released in vitro from AH-130 cells. These data suggest that the systemic effects of AH-130 tumour on the host rat reflected the interplay of a complex network of factors, including classical hormones and cytokines, all of which likely concur in enhancing tissue protein catabolism.

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Section: Humoral Mediatorsmentioning

confidence: 82%

Humoral mediation for cachexia in tumour-bearing rats

Tessitore

Costelli²,

Baccino³

1993

Br J Cancer

109

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“…However, the degree of wasting in the cancer patients used in the study was not noted, although patients ranged from those in remission to ones with advanced disease. Other workers have not found increased TNF in cancer patients [19].…”

Section: Discussionmentioning

confidence: 99%

The effects of recombinant tumour necrosis factor (cachectin) on metabolism in isolated rat adipocyte, hepatocyte and muscle preparations

Rofe

Conyers

Bais

et al. 1987

Biochemical Journal

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Tumour necrosis factor (TNF) did not stimulate lipolysis in isolated rat adipocytes, though preincubation with TNF increased adrenaline-stimulated fatty acid release. Glycogenolysis, gluconeogenesis and ketogenesis in isolated rat hepatocytes were not influenced by TNF in short-term (30-60 min) incubations. TNF stimulated 14CO2 production from [U-14C]glucose in rat hemidiaphragm preparations, but lactate production and alanine release were not significantly altered. It is concluded that TNF does not regulate short-term metabolism in adipocytes, hepatocytes and muscle preparations in the manner of a catabolic hormone.

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“…TNF levels in the remaining samples ranged in general from 2 to 300 pg/ml, and all of the patients (5/79) with TNF levels > 0.1 ng/ml died (70). In an earlier study, 3/23 septic patients were found to have TNF levels of 3-20 pg/ml (71). Tracy et al employed a skeletal muscle depolarization assay to detect picomolar levels of TNF in plasma samples of critically ill patients (72,73).…”

Section: Discussionmentioning

confidence: 99%

Participation of tumor necrosis factor in the mediation of gram negative bacterial lipopolysaccharide-induced injury in rabbits.

Mathison¹,

Wolfson²,

Ulevitch³

1988

J. Clin. Invest.

566

229

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Macrophages are induced by LPS to release a number of products that determine the host response during gram negative sepsis. To examine the role of one such substance, tumor necrosis factor (TNF), in mediating LPS-induced injury, we employed a rabbit model of endotoxic shock to (a) determine the kinetics and extent of release of TNF into plasma after injection of LPS, and (b) to evaluate the protective effect of in vivo neutralization of LPS-induced TNF by prior infusion of anti-TNF antibody. TNF was maximally induced 45-100 min after injection of 10 jig i.v. parent Salmonella Minnesota Re595 LPS or 250 ;&g Re595 LPS-HDL complexes. Maximal induction of TNF by LPS was associated with development of hypotension, focal hepatic necrosis, intravascular fibrin deposition and lethality. Based on (a) the peak levels of TNF observed in serum, 2.5 X 103 U/mIl, (b) the specific activity of purified rabbit macrophage-derived TNF, 1 X 108 U/mg, and (c) the biphasic disappearance of intravenously injected purified TNF (t1/2 = 0.5 min. 11 min) we constructed a kinetic model showing that at least 130 jig of TNF (1.3 X 107 U) was released into plasma 30-200 min postinjection of LPS. Prior infusion. of anti-TNF antibody (3045 min before LPS injection) resulted in neutralization of the LPS-induced serum TNF activity and provided significant protection from the development of hypotension, fibrin deposition, and lethality. Thus, these results provide further evidence that TNF plays a central role mediating the pathophysiologic changes that occur during gram negative endotoxic shock.

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Detection of Tumour Necrosis Factor‐Like Cytotoxicity in Serum from Patients With Septicaemia but Not from Untreated Cancer Patients

Cited by 122 publications

References 10 publications

Humoral mediation for cachexia in tumour-bearing rats

Humoral mediation for cachexia in tumour-bearing rats

The effects of recombinant tumour necrosis factor (cachectin) on metabolism in isolated rat adipocyte, hepatocyte and muscle preparations

Participation of tumor necrosis factor in the mediation of gram negative bacterial lipopolysaccharide-induced injury in rabbits.

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