Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:017444 (TNF)
 61,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Tumor necrosis factor-alpha pretreatment is protective in a rat model of myocardial ischemia-reperfusion injury. 137 34

Interleukin-1 (IL-1 beta), tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) were measured in serum from children with measles using an immunoradiometric assay. The IFN-gamma level was increased in 52 out of 54 patients in the acute phase of measles (less than 7 days of illness), and then declined to an undetectable level in the convalescent phase. Neither IL-1 nor TNF could be detected during the course of the illness. The mean serum IFN-gamma level was at its peak on day 4 and could be detected over a 7-day period after the onset of fever, coinciding with the febrile period (6.9 +/- 1.5 days). In the acute phase, the phytohaemagglutinin responses, absolute number of platelets, total lymphocyte counts, CD3+, CD4+, CD8+ cell counts and the CD4/8 ratio were depressed, while stab cell number and lactate dehydrogenase levels were higher than those in the convalescent phase. Using Spearman rank sum test, the IFN-gamma level was correlated negatively with the peripheral lymphocyte (P less than 0.01), CD3+ (P less than 0.05), CD4+ (P less than 0.05) cell counts and the CD4/8 ratio (P less than 0.05) and correlated positively with the stab cell count (P less than 0.01) but not with any other parameter. When the acute phase findings were compared between 28 complicated and 40 uncomplicated patients, the former were younger (P less than 0.01) and had higher maximum body temperature during the illness (P less than 0.05) than the latter, there was no difference in their IFN-gamma levels. These results show that endogenous IFN-gamma appears in the circulation during the acute febrile phase of measles, but does not contribute directly to any complication of the disease.
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PMID:The inflammatory cytokines in measles: correlation between serum interferon-gamma levels and lymphocyte subpopulations. 139 9

Rats were exposed to saline or cadmium chloride (CdCl2) at 25, 100, or 400 micrograms/kg body weight by intratracheal instillation. At 3, 7, 14, and 28 days after exposure five animals/treatment were euthanized, the lungs were lavaged, and bronchoalveolar lavage fluid (BALF) was analyzed for lactate dehydrogenase (LDH), total protein, N-acetylglucosamindase (NAG), and cell number, type, and viability. Lung hydroxyproline concentration was characterized as a marker of lung collagen. Alveolar macrophages (AM) obtained in BALF were cultured and the release of fibronectin and TNF was determined. Lung tissue was examined microscopically at 28 and 90 days after exposure. Exposure to CdCl2 resulted in lung injury and inflammation demonstrated by increases in BALF LDH, total protein, NAG, and inflammatory cells. AM TNF release was not significantly changed by CdCl2 treatment. All doses of CdCl2 stimulated AM fibronectin secretion, a response which persisted throughout the 28-day postexposure period examined. Pulmonary fibrosis was demonstrated biochemically and/or histologically (trichrome staining tissue) at all CdCl2 dose levels. The association of CdCl2-induced AM fibronectin release with lung fibrosis confirms and extends previous observations relating AM-derived fibronectin to the development of interstitial lung disease and provides further evidence that the persistent increase in AM fibronectin release represents an early indicator of fibrosis.
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PMID:Stimulation of rat alveolar macrophage fibronectin release in a cadmium chloride model of lung injury and fibrosis. 152 50

We examined the effects of tumor necrosis factor-alpha (TNF alpha) stimulation of endothelial cells on the increase in endothelial permeability induced by H2O2. Bovine pulmonary microvascular endothelial cells (BPMVEC) were grown to confluence on a microporous filter and the 125I-albumin clearance rate across the monolayer was determined. Pretreatment with TNF alpha (100 U/ml) for 6 h had no direct effect on transendothelial 125I-albumin permeability. However, TNF alpha pretreatment enhanced the susceptibility of BPMVEC to H2O2; that is, H2O2 (10 microM) alone had no direct effect, whereas H2O2 increased 125I-albumin permeability more than threefold when added to monolayers pretreated for 6 h with TNF alpha. Determination of lactate dehydrogenase release indicated that increased permeability was not due to cytolysis. We measured the intracellular contents of GSH and catalase to determine their possible role in mediating the increased susceptibility to H2O2. TNF alpha treatment (100 U/ml for 6 h) decreased total GSH content and concomitantly increased the oxidized GSH content, but did not alter the cellular catalase activity. The role of GSH was examined by pretreating endothelial cells with 2 mM GSH for 3 h, which produced an 80% increase in intracellular GSH content. GSH repletion inhibited the increased sensitivity of the TNF alpha-treated endothelial cells to H2O2. We tested the effects of xanthine oxidase (XO) inhibition since XO activation may be a source of oxidants responsible for the decrease in cellular GSH content. Pretreatment with 0.5 mM oxypurinol attenuated the synergistic effect of TNF alpha and H2O2 on endothelial permeability. The results indicate that decreased oxidant buffering capacity secondary to TNF alpha-induced reduction in intracellular GSH content mediates the increased susceptibility of endothelial cells to H2O2. This mechanism may contribute to oxidant-dependent vascular endothelial injury in septicemia associated with TNF alpha release.
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PMID:Tumor necrosis factor-alpha-mediated decrease in glutathione increases the sensitivity of pulmonary vascular endothelial cells to H2O2. 154 73

Exposure to recombinant human tumor necrosis factor-alpha (TNF-alpha) or calcium ionophore (A23187) for 4 h increased (P less than 0.05) lactate dehydrogenase (LDH) release from cultured bovine brain endothelial cells (EC). In contrast, treatment with endotoxin or interleukin-1 did not increase (P greater than 0.05). LDH release from brain EC. Pretreatment with tungsten decreased (P less than 0.05) xanthine oxidase activity in brain EC and decreased (P less than 0.05) LDH release from brain EC following exposure to TNF. Our results suggest that TNF-alpha injures brain microvascular EC and that this effect may be mediated by xanthine oxidase.
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PMID:Tungsten treatment prevents tumor necrosis factor-induced injury of brain endothelial cells. 154 79

Procoagulant alterations and thrombocytopenia in falciparum malaria correlate with parasitemia, serum levels of tumor necrosis factor alpha (TNF alpha), and clinical severity. Thus, heparin or acetylsalicylic acid (ASA), which are used frequently to prevent thrombosis and (in the case of ASA) to control fever, could be potentially beneficial. We randomized 97 patients with falciparum malaria into three groups: 33 patients received low-dose heparin subcutaneously, 31 received ASA intravenously, and 33 did not receive either drug. All patients received appropriate antiparasitic treatment. Eighteen of 97 patients (seven receiving heparin, five receiving ASA, and 6 in the control group) had complications upon admission. During therapy, elevated TNF alpha and lactate dehydrogenase levels and decreased platelet counts returned to normal values. Except for a minimal partial thromboplastin time prolongation with heparin, heparin or ASA did not affect any laboratory parameter, duration of parasitemia, fever clearance, or the length of hospitalization. Thus, it appears that ASA and heparin do not influence the course of falciparum malaria. Hence, in view of possible side effects, these substances should not be recommended for routine use in the treatment of human malaria.
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PMID:Neither heparin nor acetylsalicylic acid influence the clinical course in human Plasmodium falciparum malaria: a prospective randomized study. 195 71

Whole animal studies suggest that tumor necrosis factor-alpha (TNF alpha) plays a central role in the endotoxin response. In vitro studies show that TNF alpha and endotoxin induce a similar range of metabolic changes to endothelial cells. However both endotoxin- and TNF alpha-induced cytotoxicity is not a feature of all endothelial cells lines. In recent studies, the authors have shown that endotoxin causes different responses in endothelial cells taken from two levels of the lung's circulation--main pulmonary artery and lung microvasculature. Endotoxin exposure caused cell death for cells cultured from the large pulmonary artery but not for those taken from lung periphery. The present study examined the effect of TNF alpha on endothelial cells cultured from two levels of the lungs' circulation--the main pulmonary artery and the lung microvasculature. End points examined included lactate dehydrogenase (LDH), prostacyclin, and prostaglandin E2 (PGE2) release and phase contrast microscopy. Exposure to TNF alpha resulted in a dose-dependent increase in LDH release and number of detached cells for cells of the pulmonary artery, whereas cells from the microvasculature seemed unaffected. At both levels, however, TNF alpha caused increased release of both prostacyclin and PGE2. The authors conclude that TNF alpha causes different effects in endothelial cells cultured from two levels of the same organ.
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PMID:Effects of recombinant tumor necrosis factor-alpha on cultured pulmonary artery and lung microvascular endothelial monolayers. 198 72

A simple way of measuring and evaluating lactate dehydrogenase release from lysed tumor cells is described. LDH activity was determined as NADH oxidation or INT reduction over a defined time interval, which was limited by stopping the enzymatic reaction with the inhibitor oxamate. Reaction products were then assayed using a microplate reader. The principle of measuring LDH activity of cellular culture supernatants as a measure of cytotoxicity was successfully applied to a number of murine and human effector-target cell combinations (macrophages, monocytes, NK cells and cytotoxic T cells with P815, A375, K562 and Yac-1 tumor cells) as well as to the determination of TNF activity on L929 cells. Comparison with 51Cr release assays suggests that LDH release assays are an appropriate and possibly preferable means of measuring cellular cytotoxic reactions. This LDH release assay combines the advantages of reliability and simple evaluation characteristic of radioisotope release assays with the convenience of speed and avoidance of radioactivity.
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PMID:A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. 319 48

In the final two years, June 1991 to June 1993, of the Letterman Army Institute of Research, a variety of cell, tissue, organ, and animal systems were used to explore the toxicities of model hemoglobin (Hb) solutions produced in the sterile Hb production facility. Human mononuclear cells release TNF alpha and Il-8 when exposed to chromatographically purified human Hb (HbA0). Mixed cultures of fetal mouse neurons and glial cells exhibit neuronal death with exposure to HbA0 in a dose and time dependent manner while the glial cells are not injured. Isolated perfused rabbit hearts were used to explore the reversibility of coronary vasoconstriction after Hb and cyanomet-Hb administration, and deferoxamine was shown to partially protect that reversibility. In rabbits HbA0 and human Hb cross-linked with bis(3,5-dibromosalicyl) fumarate (alpha alpha Hb) caused hypertension and pulmonary arteritis. In swine, HbA0 and alpha alpha Hb caused systemic and pulmonary hypertension and a doubling of the vascular resistance that was equivalent to that seen with inhibition of nitric oxide synthesis. Elevations of creatine kinase and lactic dehydrogenase activity were observed after Hbs were infused, but not after blockade of nitric oxide synthesis. Acute renal failure seen after administration HbA0, did not appear after alpha alpha Hb. Infusion of cyanomet-alpha alpha Hb did not cause the increased vascular resistance seen after alpha alpha Hb. The infusion of 1-arginine or nitroglycerine with alpha alpha Hb did not prevent the increased vascular resistance and decreased cardiac output or allow the increased oxygen carrying capacity provided by Hb in the plasma from translating into improved oxygen delivery or improved oxygen consumption.
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PMID:Review of modified hemoglobin research at Letterman: attempts to delineate the toxicity of cell-free tetrameric hemoglobin. 749 49

The present study was undertaken to further define the role of alveolar macrophages (AM) in the pulmonary response to crocidolite fibers. Briefly, groups of 4 male F344 rats were intratracheally instilled with saline or saline suspensions of crocidolite at 2 or 20 mg/kg body weight. Animals were sacrificed 3, 7, 14, and 28 d after exposure and the lung response was characterized by analysis of bronchoalveolar lavage fluid (BALF) for markers of lung injury and inflammation. AM obtained in BALF were cultured and their production of the pro-inflammatory cytokines, tumor necrosis factor alpha (TNF alpha), and interleukin-1 (IL-1) were characterized along with fibronectin, a protein known to stimulate fibroblast migration and proliferation. Lung hydroxyproline content was determined 28 d after exposure and lung histopathology was characterized on d 28 and 90 after exposure. Crocidolite instillation resulted in transient dose-related pulmonary inflammation as evidenced by increased numbers of BALF neutrophils at the low dose and neutrophils, macrophages, and lymphocytes at the high dose. Cytotoxicity and increased permeability were demonstrated by increased levels of BALF lactate dehydrogenase (LDH) and total protein, respectively. AM TNF alpha and IL-1 production were increased only at the high crocidolite dose. This cytokine response was greatest at d 3 and decreased thereafter. AM TNF alpha and IL-1 release were positively correlated with the increased BALF neutrophils. In contrast to TNF alpha and IL-1, AM fibronectin release was increased at both the low and high doses, with the magnitude of response increasing over time. Consistent with previous acute asbestos inhalation studies, histopathology revealed inflammation localized at the level of the terminal bronchioles and alveolar ducts. Fibrosis was demonstrated at both doses by increased trichrome staining of lung tissue sections. Only the high dose resulted in a detectable increase in lung hydroxyproline. Given the bioactivities of TNF alpha, IL-1, and fibronectin, their increased production after crocidolite exposure indicates they contribute to the pulmonary inflammation and fibrosis occurring with this mineral fiber. In addition, the correlation of increased AM TNF alpha and IL-1 production with increased BALF neutrophils supports a role for these cytokines in crocidolite-induced inflammatory cell recruitment. Lastly, association of a persistent increase in AM fibronectin production with an eventual increase in lung collagen deposition extends the growing database indicating this response is a predictive marker of pulmonary fibrosis.
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PMID:Alveolar macrophage cytokine and growth factor production in a rat model of crocidolite-induced pulmonary inflammation and fibrosis. 756 15


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