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At least 1,081 records · Page 60Linked to original sources
PubMed1998

Neutralization of pyrogen-induced tumour necrosis factor by its type 1 soluble receptor in guinea-pigs: effects on fever and interleukin-6 release.

1. A soluble form of the tumour necrosis factor (TNF) type 1 receptor (referred to as TNF binding protein, TNF-bp) at a dose of 1 mg per animal, or an equivalent volume of solvent, was injected together with 10 microg kg-1 lipopolysaccharide (LPS) or 50 microg kg-1 muramyl-dipeptide (MDP) directly into the arterial circulation of guinea-pigs and the effects on circulating TNF or interleukin-6 (IL-6) and on abdominal temperature were studied. 2. At 15 or 60 min after injection, LPS-induced and MDP-induced circulating TNF was below the detection limit of the assay and thus completely neutralized in animals treated with TNF-bp. In the control group, TNF was still below the limit of detection in most animals 15 min after LPS was injected; in some animals small traces of TNF could already be detected at that time. However, 60 min after administration of LPS, large amounts of TNF (19508 +/- 4682 pg ml-1) were measured in the control group. MDP-induced TNF in plasma was below the limit of detection 15 min after MDP was injected, and rose to 10862 +/- 3029 pg ml-1 60 min after injection. 3. Low levels of circulating IL-6 (20-40 international units (IU) ml-1) were measured in all groups of animals 15 min after injection of LPS or MDP. This value corresponds to the baseline activity of IL-6 in plasma of guinea-pigs. One hour after administration of LPS, IL-6 rose to 5442 +/- 1662 IU ml-1 in the control group and to a significantly lower value of 1485 +/- 179 IU ml-1 in guinea-pigs treated with TNF-bp. One hour after injection of MDP, circulating IL-6 was 2614 +/- 506 IU ml-1 in the control group, while the corresponding value in animals treated with TNF-bp again was significantly lower (873 +/- 312 IU ml-1). 4. The second phase of the characteristic biphasic LPS fever in guinea-pigs was significantly attenuated in animals treated with TNF-bp. The shorter first phase of the febrile response to LPS was identical in both groups of animals. 5. The late phase of MDP-induced fever (7-22 h after injection) was depressed by treatment with TNF-bp, while the first phase of MDP-induced fever (0-7 h after injection) was significantly enhanced by the neutralization of TNF by TNF-bp.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

Hollow-fiber dialyzers and their pyrogenicity testing by Limulus amebocyte lysate.

Aqueous extracts of cellulose hollow fibers (CHF) exhibit positive reactions in some Limulus amebocyte lysate (LAL) tests. However, in spite of LAL activity, the extracts produce no fever reaction in rabbits. A comparison of lysates from different suppliers shows pronounced activity differences when extracts of cuprammonium-derived CHF are tested. One of the lysates, which is fully reactive against standard endotoxin, shows no reaction with such extracts, nor do CHF extracts diminish its sensitivity to standard endotoxin. Investigations of the cuprammonium process have shown that endotoxins introduced by the linters are degraded and washed out. Other endotoxin introduction, particularly by the process water, has been excluded. Oxidative or acidic degradation of cellulose does not result in the formation of LAL-reactive material (LAL-RM). On the other hand, sterile cotton wool shows LAL reactivity, and cellulose acetate regains LAL reactivity when it is saponified. Thus, it appears likely that the LAL-RM found in CHF is of purely cellulosic origin and crossreacts with a number of commercially available lysates.

Animals↗
PubMed1998

Tolerance to pyrogens.

In humans or experimental animals, the repeated confrontation with lipopolysaccharides (LPS) from gram-negative bacteria, but not with muramyl dipeptide (MDP) from gram-positive bacteria, leads to attenuation of almost all pathophysiologic effects mediated by proinflammatory cytokines. Our experiments in guinea pigs and rats demonstrate that attenuation of the febrile response during the development of LPS tolerance is associated with a reduced production of cytokines rather than a decrease in responsiveness to cytokines. Cross-tolerance experiments demonstrate that different stimuli influencing LPS-induced tumor necrosis factor (TNF) release and nitric oxide (NO) synthesis can modify the development of tolerance. On the other hand, the lack of cross-tolerance between LPS and MDP indicates that MDP can activate the cytokine cascade and induce the febrile response in animals tolerant to LPS. This may indicate distinct receptors and signal pathways for LPS and MDP, leading to activation of the cytokine cascade. LPS tolerance has also been demonstrated in ex vivo and in vitro studies. In cultures of monocytes, diminished synthesis of TNF and NO reported after LPS restimulation could be prevented and reversed by interferon and granulocyte-macrophage colony-stimulating factor. These findings add an additional hypothesis in tolerance development.

Acetylmuramyl-Alanyl-Isoglutamine↗