Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: HUMANGGP:009512 (tumor necrosis factor)
 58,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hydroxyl radical (OH.) scavenger dimethyl sulfoxide (DMSO) was found to dose-dependently inhibit interleukin 8 (IL-8) production in LPS-stimulated human whole blood. At a concentration of 1% (vol/vol), DMSO blocked IL-8 release by approximately 90% in the presence of 1 microgram/ml LPS at a 24-h time point, but did not affect cell viability or reduce the production of tumor necrosis factor (TNF), interleukin 6, or interleukin-1 beta (IL-1 beta). DMSO was found to directly inhibit IL-8 expression at the level of transcription. Furthermore, this effect was not LPS-specific, in that IL-8 production was reduced by DMSO to a similar extent upon stimulation of blood with phytohemagglutinin, aggregated immune complexes, TNF, or IL-1 beta. Other oxygen radical scavengers that have been shown to inhibit OH.-dependent reactions (dimethyl thiourea, thiourea, mannitol, and ethanol) also inhibited IL-8 production. Conversely, addition of H2O2 caused a dose-dependent stimulation of IL-8 release. These results provide evidence that reactive oxygen metabolites play an important role in the regulation of IL-8 production and suggest that reduction of IL-8 release may contribute to the beneficial effects of antioxidants in experimental models of inflammation and ischemia/reperfusion injury.
 ...
PMID:Oxygen radical scavengers selectively inhibit interleukin 8 production in human whole blood. 133 Nov 81

We have demonstrated that tumor necrosis factor-alpha (TNF-alpha) pretreatment protected the rat heart from ischemia-reperfusion injury. This effect was monitored by assaying for lactate dehydrogenase (LDH), an enzyme whose release correlates with loss of cell membrane integrity. Intact hearts removed from rats pretreated with TNF-released significantly lower amounts of LDH compared to control hearts after 20 min. of total global ischemia followed by reperfusion. Hearts from TNF-alpha-pretreated animals contained higher levels of manganous superoxide dismutase (MnSOD) mRNA than hearts from untreated rats. Because oxygen free radicals have been implicated as a major cause of reperfusion damage and the function of MnSOD is to detoxify superoxide anions in the mitochondria, a possible protective mechanism for TNF-alpha may be to induce expression of MnSOD in the heart and thus confer resistance to oxygen free radicals generated during reperfusion.
 ...
PMID:Tumor necrosis factor-alpha pretreatment is protective in a rat model of myocardial ischemia-reperfusion injury. 137 34

The effect of pretreatment with FK506 on renal ischemia and reperfusion (I/R) injury was investigated using a rat model. Animals were assigned to one of two groups (20 rats each). Group 1 animals (controls) received 0.5 ml saline while group 2 animals received FK506 (0.3 mg/kg), administered intravenously 24 hr prior to the induction of renal ischemia. A 60-min period of ischemia of the right kidney was induced, and upon reperfusion a left nephrectomy was performed. Blood samples for estimation of BUN, creatinine, and tumor necrosis factor were collected on days 0 (preischemia), 1, 2, 3, 5, 7, and 10 (postischemia). Rats were sacrificed after day 10 and renal tissue was examined histologically. All animals survived the ischemic episode. FK506 pretreatment significantly reduced the serum levels of BUN (P less than 0.02), creatinine (P less than 0.02), and TNF (P less than 0.05) as compared with that seen in controls. Histologically, at day 10, the kidneys showed the expected sequelae of prior renal I/R with various degrees of tubular damage. However, no objective differences were evident between the two groups. Based upon these data, it can be concluded that (1) FK506 pretreatment ameliorates the functional renal injury associated with I/R, (2) renal ischemia induces the release of TNF, and (3) FK506 pretreatment results in a significant inhibition of TNF production. These data suggest that the release of TNF may be responsible for the increasing of BUN and creatinine levels seen after renal I/R and that pretreatment of renal donors with FK506 may improve renal function in the immediate post-transplant period.
 ...
PMID:The protective effect of FK506 pretreatment against renal ischemia/reperfusion injury in rats. 137 48

The effect of FK 506 pretreatment on renal ischemia and reperfusion (I/R) injury was investigated. Adult male rats were assigned to one of two groups (20 animals each). Group 1 (controls) received 0.5 mL saline while group 2 received FK 506 (0.3 mg/kg) intravenously 24 h prior to the induction of renal ischemia. After a 60-min period of ischemia of the right kidney, a left nephrectomy was performed. Blood for BUN, creatinine, and tumor necrosis factor (TNF) was obtained prior to ischemia and on days 1, 2, 3, 5, 7, and 10. All surviving animals were sacrificed at day 10. FK 506 pretreatment reduced the serum levels of BUN (p less than .02), creatinine (p less than .02) and TNF (p less than .05) as compared to that seen in controls. Based upon these data, it appears that: (a) renal ischemia induces the release of TNF; (b) FK 506 pretreatment inhibits TNF production; and (c) FK 506 reduces renal injury association with I/R.
 ...
PMID:FK 506 reduces the injury experienced following renal ischemia and reperfusion. 138 Jul 20

Cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF) are known to mediate host cell response to sepsis, trauma, and myocardial ischemia. We have previously found increased levels of IL-1 in the venous effluent during the reperfusion phase of skeletal muscle ischemia in a canine model. This study was done to evaluate whether TNF also played a role in skeletal muscle ischemia-reperfusion injury since IL-1 and TNF have inter-related functions. In twelve adult mongrel dogs (28-32 kg) one gracilis muscle was subjected to six hours of normothermic ischemia followed by normothermic reperfusion. The contralateral side served as a control and remained normally perfused throughout the experiment. Gracilis venous samples were collected at pre-ischemia and one hour of reperfusion. Systemic (arterial) blood samples were taken simultaneously with the venous samples at one hour of reperfusion. At the end of the experiment the muscles were harvested and amount of necrosis quantitated by serial transections, nitroblue tetrazolium staining and computerized planimetry. Muscle necrosis on the experimental side was found to be 48.86 +/- 5.37%. Sera were analyzed for TNF activity using a bioassay. TNF levels in the gracilis venous effluent at one hour of reperfusion were not significantly different from the simultaneous systemic (arterial) levels (27.15 +/- 5.05 pg/ml vs 18.23 +/- 4.27 pg/ml). Pre-ischemic levels of TNF were 96.50 +/- 20.12 pg/ml, which was significantly higher than either venous or arterial levels obtained after one hour of reperfusion (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Do cytokines play a role in skeletal muscle ischemia and reperfusion? 144 79

We studied the ex vivo secretion of tumor necrosis factor (TNF) and interleukin 2 (IL-2) by splenocytes after circulatory shock induced by intestinal ischemia and reperfusion in rats. Shock was induced by total occlusion of the superior mesenteric artery followed by reperfusion. In a second group, vascular occlusion was maintained throughout the experimental protocol. A third group of sham rats and a fourth group of control rats with a negligible surgical procedure were also studied. "Spontaneous" (untriggered) secretion of TNF by splenocytes was higher in the ischemia-reperfusion group than in all other groups (p < 0.01), but did not increase significantly after stimulation with LPS. Splenocytes from control rats exhibited a marked increase in TNF secretion after stimulation with LPS to values similar to those in the ischemia-reperfusion group. A diminished, though statistically significant increase in LPS-stimulated secretion of TNF was detected in the sham and ischemia only groups of rats (p < 0.05) from untriggered values in each. Untriggered secretion of IL-2 was similar in all groups. However, when compared to control rats, splenocytes from the three surgically manipulated groups exhibited suppressed secretion of IL-2 in response to stimulation with Con A (p < 0.05). These results support the role played by TNF in mediation of shock and point to spleen macrophages as a source of TNF after intestinal ischemia and reperfusion. Our results also demonstrated postinjury alteration in immune function manifested by depressed ability of splenocytes to increase the production of IL-2 after stimulation with Con A.
 ...
PMID:Ex vivo secretion of tumor necrosis factor and interleukin-2 by rat splenocytes after intestinal ischemia and shock. 146 63

Experimental studies have shown that liver ischemia-reperfusion induces Kupffer cell activation and tumor necrosis factor-alpha (TNF alpha) release. The aim of this work was to determine whether severe hepatic ischemia and subsequent reperfusion triggers TNF alpha release in man. Serum TNF alpha was measured before and 3, 10, 30, 60, 120 min after revascularization and postoperatively at day 1 and 2 in 11 patients with orthotopic liver transplantation (group 1) and 4 patients with liver resection with vascular occlusion (group 2). In group 1, TNF alpha levels decreased during the first few minutes of reperfusion, then increased slightly to peak at 120 min (40 +/- 13 pg/ml). Primary non-function occurred in 1 patient in whom low peroperative levels of TNF alpha levels were measured. In group 2, no significant changes in TNF alpha levels were observed. These data, in a small number of patients: (a) show that hepatic ischemia-reperfusion does not result in major TNF alpha production; (b) do not support a primary pathogenic role for TNF alpha in damage after ischemia-reperfusion in humans.
 ...
PMID:Tumor necrosis factor-alpha in liver transplantation and resection. No evidence for a key role in ischemia-reperfusion injury. 148 16

The potassium channel activator nicorandil, under evaluation for antianginal management, has been shown to decrease neutrophil respiratory burst. Since our laboratory has demonstrated that reactive oxygen species (ROS) increase tumor necrosis factor (TNF) production, we hypothesized that nicorandil might decrease TNF production from a lipopolysaccharide (LPS) challenge via reduction of respiratory burst. Macrophage viability and TNF production were determined after an 18-hr exposure to 5.0 micrograms/ml LPS and varying concentrations of nicorandil. Nicorandil was not toxic to macrophages below 12 mM (94 +/- 3% viability versus control) and decreased ROS and TNF production. Intracellular superoxide production decreased from 164 +/- 24 OD550 to 99 +/- 6 OD550 with 10 mM nicorandil and extracellular superoxide decreased from 3108 +/- 111 to 1760 +/- 210 nM. Hydrogen peroxide production was also decreased by 10 mM nicorandil. TNF production in response to 5 micrograms/ml LPS decreased from 6.8 +/- 0.6 to 2.7 +/- 0.4 ng/ml with 10 mM nicorandil. Northern and slot blot analyses demonstrate that nicorandil acts at a post-transcriptional site. These data imply that nicorandil decreases macrophage TNF production from an LPS challenge, possibly through a reduction in respiratory burst. Such compounds may prove useful in the treatment of conditions thought to be associated with free radical-lymphokine interactions such as ischemia-reperfusion injury, oxygen toxicity, adult respiratory distress syndrome, and septic shock.
 ...
PMID:Alterations in macrophage free radical and tumor necrosis factor production by a potassium channel activator. 153 87

In the past few years tumor necrosis factor (TNF), also known as cachectin, has been isolated, cloned and now human recombinant TNF is available. This cytokine has numerous actions, which can be divided into four groups: 1) antitumor function; 2) immunomodulating activity and function in the inflammatory response; 3) effects on metabolism; 4) other functions. TNF was first identified for its anticancer activity; it is able to induce hemorrhagic necrosis in subcutaneously implanted tumors, due to the induction of free radicals in tumor cells and to vascular damage. It can also activate T-lymphocytes to become lymphokine-activated killer cells (LAK cells) against tumors. TNF also plays an important role in the inflammatory response: it mediates many of the immunologic features of T-cell function and of infection, and is essential in septic shock. TNF is a cause of the hypertriglyceridemia and the cachexia that characterize chronic infections and neoplasms. In vitro this cytokine causes growth of vascular endothelial cells; this observation suggests that it could have an atherogenic role. In in vivo experiments severe hepatic ischemia-reperfusion injury results in TNF release with subsequent local and systemic injury that was significantly reduced by anti-TNF antiserum pretreatment. Thus, TNF could be a cause of ischemic tissue damage. In conclusion, while TNF is known to play many roles, the intercellular network of the cytokines is not yet sufficiently understood and so we are only just beginning to comprehend the full implication of this important molecule in both histology and pathology.
 ...
PMID:[Tumor necrosis factor: a cytokine with multiple actions]. 156 77

Interleukin-8 (IL-8) belongs to a family of small, structurally related cytokines similar to platelet factor 4. It is produced by phagocytes and mesenchymal cells exposed to inflammatory stimuli (e.g., interleukin-1 or tumor necrosis factor) and activates neutrophils inducing chemotaxis, exocytosis and the respiratory burst. In vivo, IL-8 elicits a massive neutrophil accumulation at the site of injection. Five neutrophil-activating cytokines similar to IL-8 in structure and function have been identified recently. IL-8 and the related cytokines are produced in several tissues upon infection, inflammation, ischemia, trauma etc., and are thought to be the main cause of local neutrophil accumulation.
 ...
PMID:Interleukin-8, a chemotactic and inflammatory cytokine. 163 1


1 2 3 4 5 6 7 8 9 10 Next >>