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

Acute respiratory failure in pregnancy is an important cause of maternal and fetal morbidity and mortality. Causes include: ARDS, venous air embolism, beta-adrenergic tocolytic therapy, asthma, thromboembolic disease, pneumothorax, and pneumomediastinum. The most common predisposing diseases for ARDS complicating pregnancy are sepsis, pneumonia, aspiration of gastric contents, and amniotic fluid embolism. Knowledge of normal maternal-fetal physiology and determinants of fetal oxygen delivery (uterine blood flow, placental transfer, fetal circulation) can help sustain normal fetal development, usually without compromising maternal care. The increased microvascular permeability seen in ARDS is likely mediated by neutrophils, proinflammatory mediators (e.g., tumor necrosis factor, interleukin-1, arachidonic acid metabolites) and activation of the complement cascade. Treatment of respiratory failure in pregnancy is largely supportive, including mechanical ventilation, hemodynamic support, nutrition, and prophylaxis against thromboembolism. No specific therapy has as yet been proven effective for ARDS, other than treating the underlying cause. Respiratory failure from status asthmaticus is treated with vigorous bronchodilator therapy, high-dose glucocorticosteroids, magnesium sulfate, and careful ventilator management. Occasionally, more experimental therapies (e.g., isoproterenol infusion, halothane anesthesia) are indicated. Certain strategies can help prevent respiratory failure from aspiration of gastric contents, beta-adrenergic tocolytic therapy, and thromboembolic disease.
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PMID:Acute respiratory failure in pregnancy. 136 44

We investigated alterations in myocardial beta- and beta 1-adrenergic receptor (BAR and B1AR) number during hyperdynamic state induced by endotoxin or cytokines. [METHODS] Twenty-nine Japanese White rabbits were divided into 2 groups. Hearts were removed 18 h after intraperitoneal administration of sterile saline (SAL) or E. coli endotoxin (LPS; 50 micrograms/kg) (Group E, n = 12), or 3 h after intravenous injection of SAL or cytokines (interleukin 1-beta; 5 micrograms/kg followed by 25 ng/kg/min for 2 h, or tumor necrosis factor; 5 micrograms/kg) (Group C, n = 17). BAR and B1AR numbers were determined in myocardial membranes from rabbit left ventricles with techniques of radioactive ligand binding study. We used [3H] dihydroalprenolol (3H-DHA) as radioactive ligand, and specific 3H-DHA binding to BARs was defined as the difference between the presence and the absence of 10 microM propranolol. B1AR number was assessed through the specific binding of 3H-DHA in the presence of ICI 118, 551 (5 x 10(-8) M), a highly selective beta 2-adrenergic receptor antagonist. In Group E, mean arterial blood pressure (MAP), heart rate (HR), and cardiac output (CO) (by thermodilution) were measured under pentobarbital sodium anesthesia before excision of hearts. [RESULTS] In Group E, CO was significantly (p less than 0.05) increased in rabbits injected with LPS (E-LPS) as compared with that in rabbits injected with SAL (E-SAL) (E-LPS; 0.75 +/- 0.02 l.min-1, E-SAL; 0.61 +/- 0.05 l.min-1, mean +/- SEM). MAP and HR were slightly decreased in E-LPS but not significantly. Maximum binding (Bmax) of 3H-DHA to BARs was significantly (p less than 0.05) decreased by 18% in myocardial membranes from E-LPS compared to E-SAL (E-LPS; 48.2 +/- 4.3 fmol/mg protein, E-SAL; 58.9 +/- 2.9 fmol/mg protein, mean +/- SEM). Similarly, Bmax of 3H-DHA to B1ARs was decreased by 18% in E-LPS, although no statistical significance was detected. In Group C, both BAR and B1 AR number was slightly, but not significantly decreased 3 h after administration of cytokines. [CONCLUSION] These data suggest that down regulation of cardiac BARs may occur during hyperdynamic stage of endotoxic shock.
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PMID:[Alterations in number of rabbit myocardial beta-adrenergic receptors in endotoxic shock: down regulation in hyperdynamic sepsis model and effects of cytokines administration]. 166 39

To investigate the possible hemodynamic effects of interleukin-6 (IL-6), a single dose of 15 mcg/kg of recombinant IL-6 isolated from Escherichia coli was injected intravenously in six pentobarbital-anesthetized dogs. After 30 min, saline infusion was performed to maintain the pulmonary artery balloon-occluded pressure at baseline level. The animals were observed for up to 5 hours. No other hemodynamic alteration was observed than a gradual decline in cardiac output attributed to anesthesia. Hematologic variables, blood glucose, and total serum proteins were also constant. IL-6 levels were markedly elevated in the blood, but no tumor necrosis factor activity was detected. Thus a primary role for IL-6 in the early cardiovascular alterations associated with septic shock seems unlikely.
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PMID:Interleukin-6 administration has no acute hemodynamic or hematologic effect in the dog. 188 51

The progression to somatic death after brain death is poorly understood. The role of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in this progression is unknown. TNF-like and IL-6-like plasma activities were assayed in a canine model of brain death in the presence and absence of a lipopolysaccharide (LPS) challenge (0.22 micrograms/kg). Bioassays for TNF-like and IL-6-like activities used WEHI and B9 cell lines, respectively. Brain death was induced by elevating and maintaining intracranial pressure above systolic arterial pressure. Anesthesia and the operative procedure did not cause a significant increase of either cytokine. Brain death (n = 8) itself did not cause a significant elevation of either cytokine compared with the sham brain-death control (n = 6) despite a significant decrease in mean arterial pressure (35 +/- 3 vs. 115 +/- 5 mmHg at 5 h). The brain-dead group treated with LPS (n = 6) responded with a significant elevation in IL-6-like and TNF-like activities compared with the vehicle-treated group. The rise of IL-6-like activity in response to LPS was greater in the brain-dead group than in the sham brain-dead group (n = 3); no significant difference was noted for the TNF-like response. We conclude that the progression to somatic death after brain death cannot be explained by increases in circulating TNF-like or IL-6-like activities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma profiles of IL-6-like and TNF-like activities in brain-dead dogs. 195 61

The influence of sedative and anxiolytic benzodiazepines on human monocyte function was assessed in 11 patients undergoing anesthesia prior to control endoscopy of the urinary tract. A single i.v. injection of 0.08 mg/kg midazolam induced a marked and delayed inhibition of the lipopolysaccharide-induced production of interleukin-1 beta, tumor necrosis factor-alpha and interleukin-6 by monocytes isolated from peripheral blood. Corticosteroids were not responsible for the observed immunosuppression. These studies demonstrate that, when administered in man, benzodiazepines markedly alter the capacity of monocytes to synthetize major mediators of the host inflammatory response.
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PMID:Benzodiazepine anesthesia in humans modulates the interleukin-1 beta, tumor necrosis factor-alpha and interleukin-6 responses of blood monocytes. 195 61

The effect of blood transfusions and anesthesia on host response to endotoxin was evaluated in multiple Lewis rat models. The rats were randomized to receive A'Sogaloff Cancer Institute rat blood, pentobarbital sodium, or lactated Ringer's solution and, at either 2 or 7 days following administration of these agents, were challenged with intravenous endotoxin. Neither blood transfusions nor anesthesia altered mortality when administered 2 days before endotoxin challenge. However, blood transfusions administered 7 days before endotoxin challenge were found to prolong survival, to prevent endotoxin-induced alterations in T-lymphocyte subsets, and to decrease plasma tumor necrosis factor levels. In conclusion, blood transfusions appear to depress immune function in a beneficial manner in endotoxin shock.
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PMID:Alterations in host defense associated with anesthesia and blood transfusions. II. Effect on response to endotoxin. 198 35

The purpose of this study was to support the hypothesis that cytokines such as interleukin-1, tumor necrosis factor and interleukin-6 are released by macrophages or monocytes within 1 to 2 hr of phagocytosis of circulating, gut-derived bacterial lipopolysaccharide translocated by acute liver injury. Time courses of fever, neutrophilia and low blood-zinc levels generally attributed to cytokines were quantified after partial (67%) hepatectomy of rats under ether anesthesia. These acute phase responses in hepatectomized rats were compared with those after intravenous injection of exogenous endotoxin and human natural interleukin-1. Fever commenced 30 min after interleukin-1 injection, 4 hr after exogenous lipopolysaccharide injection and 6 hr after 67% liver resection. Similarly, rectal temperatures were significantly elevated in recipient rats 30 min after intravenous administration of donor plasma from hepatectomized animals, indicating that cytokines, not lipopolysaccharide, elicited the febrile response. Neutrophilia was present 1, 2, and 4 hr after interleukin-1 injection, lipopolysaccharide injection and hepatectomy, respectively. Furthermore, the reduction in plasma zinc, which depends on cellular metallothionein synthesis, occurred 4 hr after interleukin-1 administration and 6 hr after lipopolysaccharide injection or partial hepatectomy. Donor plasma from hepatectomized rats also elicited neutrophilia at 1 hr and low blood-zinc levels 4 hr after injection in recipient animals. The timing of these responses, just as for the fever, implies that cytokines and not lipopolysaccharide in the donated plasma elicited the neutrophilia and hypozincemia. Evidence was reviewed that interleukin-1, tumor necrosis factor and interleukin-6 function as hepatotrophic factors and have been identified in the circulation of humans with liver damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute phase responses after acute liver injury by partial hepatectomy in rats as indicators of cytokine release. 211 49

The hypothesis was tested that alcohol may modulate alveolar macrophage cytokine receptors, thus interfering in lung immune defense mechanisms. Male rats were treated with alcohol either acutely (7 hr continuous intravenous alcohol infusion at a rate of 30 mg/100 g body weight/hr after a priming dose of 175 mg/100 g body weight) or chronically (feeding an alcohol-containing liquid diet for 12-14 weeks). Three hr before killing, the rats received an intravenous injection of Gram-negative bacterial lipopolysaccharide (LPS; Escherichia coli, O26:B6, 100 micrograms/100 g body weight). After anesthesia with sodium pentobarbital, the trachea was cannulated, and the lungs excised and lavaged to obtain alveolar macrophages. The recovered cells were used to measure the binding of recombinant human [125I]tumor necrosis factor-alpha (TNF-alpha) and [125I]interleukin-6 (IL-6). Kd and Bmax were determined at 4 degrees C, thus reflecting only the cell-surface binding sites and their affinity. Two binding sites were detected for both cytokines: high-affinity (Kd1 in the range of 20-110 pM), low-capacity (Bmax1 in the range of 1-13 fmol/10(6) cells), and low-affinity (Kd2 in the range of 0.6-1.3 nM), high-capacity (Bmax2 in the range of 34-100 fmol/10(6) cells). Acute alcohol treatment significantly decreased Bmax1 (39%) and Bmax2 (79%) for TNF-alpha, whereas chronic alcohol feeding abrogated the Bmax1 (Bmax1 = 0), without affecting Bmax2. In the acute group, LPS had an effect similar to that of alcohol. Alcohol administration did not modify the LPS effects. The following changes were monitored for IL-6 binding. Acute alcohol treatment markedly reduced (86%) Bmax2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of tumor necrosis factor-alpha and interleukin-6 cell-surface receptors of the alveolar macrophage in alcohol-treated rats. 769 40

The proinflammatory cytokines have been implicated in mediating myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. We tested the hypothesis that cytokine levels are elevated after uncomplicated coronary artery bypass grafting and associated with episodes of postoperative myocardial ischemia and dysfunction. Coronary artery bypass grafting was performed under general anesthesia with moderate systemic hypothermia and cold-blood potassium cardioplegic solution. Tumor necrosis factor-alpha and interleukin-6 levels were determined by bioassays, and interleukin-8 levels were measured by a sandwich enzyme-linked immunosorbent assay. Myocardial function and ischemic episodes were assessed by intraoperative transesophageal echocardiography and perioperative 12-channel Holter monitoring. A total of 22 patients were studied, with no deaths or complications. Arterial tumor necrosis factor-alpha rose in a bimodal distribution, peaking at 2 and 18 to 24 hours after the operation (at 20.2 +/- 6.4 pg/ml, [mean +/- standard error of the mean]) and 5.8 +/- 1.6 pg/ml, respectively; before cardiopulmonary bypass: 0.90 +/- 0.20 pg/ml, p < 0.001 for both peaks) then progressively declined to levels before bypass. Arterial interleukin-6 was maximally elevated immediately on termination of cardiopulmonary bypass and peaked again 12 to 18 hours after cardiopulmonary bypass (at 7520 +/- 2439 pg/ml and 6216 +/- 1928 pg/ml, respectively; before bypass: 746 +/- 187 pg/ml, p < 0.0001 for both peaks). Arterial interleukin-8 levels were more variable but followed a similar pattern, peaking in the early period after cardiopulmonary bypass and again at 16 to 18 hours after the operation (at 4110 +/- 1403 pg/ml and 1760 +/- 1145 pg/ml, respectively; before bypass: 461 +/- 158, p < 0.05 for both peaks). By multivariate analysis, the aortic crossclamp time was independently predictive of postoperative cytokine levels. Left ventricular wall motion abnormalities were associated with both interleukin-6 and interleukin-8 levels, worsening scores being associated with increasing levels (for interleukin-6, p = 0.003; for interleukin-8, p = 0.05). Postoperative myocardial ischemic episodes were associated with interleukin-6 levels, six of seven (85%) patients with episodes of myocardial ischemia after a peak in interleukin-6 concentrations (p < 0.01). We conclude that proinflammatory cytokines are elevated after uncomplicated coronary revascularization and may contribute to postoperative myocardial ischemia and segmental wall motion abnormalities.
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PMID:Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. 793 95

Guinea pigs were passively sensitized with immune serum to ovalbumin (OA), control serum, or saline. Twenty-four hours later, they inhaled aerosols of OA (2% in saline), saline, or lipopolysaccharide (LPS). Following anesthesia, bronchoalveolar lavage (BAL) was performed at 30, 60, 90 and 120 min postinhalation. Alveolar macrophages (AM) were isolated from the BAL fluid and incubated (18 h) in medium alone or with zymosan (1 mg/ml). Supernatants were collected and levels of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) determined by bioassays. Unstimulated AM from animals that inhaled OA, saline, or LPS secreted similar amounts of IL-1 at 30, 60, and 90 min postinhalation. Zymosan (1 mg/ml) significantly increased IL-1 secretion by AM collected at 60 and 90 min from OA-sensitized animals that inhaled OA or saline. AM from guinea pigs sensitized to OA that inhaled OA or LPS secreted significantly increased amounts of IL-6 at 30, 60, 90, and 120 min postchallenge compared to saline sensitized controls. In all groups, AM from LPS-treated animals secreted large amounts of TNF-alpha at all sampling times postchallenge; AM from OA-sensitized and challenged animals secreted increasing amounts of TNF-alpha with time postchallenge, spontaneously and in response to zymosan. By contrast, AM from saline sensitized and challenged guinea pigs did not release detectable amounts of TNF-alpha spontaneously and secreted very low amounts in the presence of zymosan. These findings show that antigen challenge results in a rapid activation of AM isolated from BAL and suggest AM may initiate the development of inflammatory processes associated with antigen challenge.
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PMID:Release of monokines by pulmonary macrophages following antigen challenge in sensitized guinea pigs. 798 26


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