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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adult respiratory distress syndrome is an inflammatory disorder of the lung parenchyma that results in severe respiratory failure. It is associated with sepsis syndrome and multiple organ failure and may be mediated by a variety of substances, several of which have been discussed in this article. Because sepsis syndrome, ARDS, and multiple organ failure are associated with a high mortality rate that has not been reduced significantly by supportive treatment, a rationale exists for therapeutic intervention with agents that affect the inflammatory cascade. Several of these agents, notably corticosteroids and prostaglandin E1, have been shown to be of no benefit in humans despite laboratory and animal studies suggesting their utility. Other agents, including surfactant, antiendotoxin antibodies, and NSAIDs, are undergoing clinical trials and may prove to be effective. A third group, including anti-TNF antibodies and pentoxifylline, are of theoretical benefit but await clinical trials.
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PMID:Pharmacologic treatment of the adult respiratory distress syndrome. 226 1

Fibrin formation plays an important role in glomerular injury. We therefore examined the procoagulant signal produced by cultured rat mesangial cells. Actively growing mesangial cells produced procoagulant activity (PCA) that was present in intact cells (surface-associated), was inhibitable by cyclohexamide and which, by clotting assay, had the characteristics of tissue factor. This PCA decreased with incubation of cells in serum-deprived medium. Incubation with bacterial lipopolysaccharide (LPS) and tumor necrosis factor (TNF alpha) induced increased detectable tissue factor by mesangial cells within two hours which was maximal by four hours. We conclude that quiescent mesangial cells produce a small amount of tissue factor-like procoagulant activity, and that this PCA can be stimulated by incubation with TNF alpha, LPS or when cells are actively growing in high serum medium. Therefore mesangial cells have the capability of contributing to fibrin formation during inflammatory glomerular injury or sepsis.
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PMID:Tissue factor production by cultured rat mesangial cells. Stimulation by TNF alpha and lipopolysaccharide. 234 26

Intestinal mucosal atrophy, as induced by total parenteral nutrition (TPN) and/or prolonged bowel rest, is hypothesized to enhance bowel endotoxin (LPS) translocation and may alter host responses to infection. To examine the effect of TPN-induced bowel atrophy on the response to LPS, 12 healthy volunteers were randomized to receive either enteral feedings (ENT, n = 6) or seven days of TPN without oral intake (TPN, n = 6). Enteral or TPN feedings were terminated 12 hours before the study period when a constant dextrose infusion (50 mg/kg/hour) was initiated and continued throughout the subsequent study period. After placement of arterial, hepatic vein, and femoral vein catheters, metabolic parameters were determined before and for six hours after an intravenous E. coli LPS challenge (20 U/kg). Subsequent peak levels of arterial glucagon (ENT, 189 +/- 39 pg/mL; TPN, 428 +/- 48; p less than 0.01), arterial epinephrine (ENT, 236 +/- 52 pg/mL; TPN, 379 +/- 49; p less than 0.05) and hepatic venous cachectin/tumor necrosis factor (cachectin/TNF) (ENT, 250 +/- 56 pg/mL; TPN, 479 +/- 136; p less than 0.05) were significantly higher in the TPN group than in the ENT group. The extremity efflux of lactate (ENT, -16 +/- 4 micrograms/min-100cc tissue; TPN, -52 +/- 13; t = 2 hours; p less than 0.05) and of amino acids (ENT, -334 +/- 77 nmol/min-100cc tissue; TPN, -884 +/- 58; t = 4 hours; p less than 0.05) were higher in the TPN subjects after the endotoxin challenge. Circulating C-reactive Protein (CRP) levels measured 24 hours postendotoxin were also significantly higher in the TPN subjects (ENT, 1.7 +/- 0.2 mg/dL; TPN, 3.2 +/- 0.3; p less than 0.01). Hence the counter-regulatory hormone and splanchnic cytokine responses to LPS were enhanced after TPN and bowel rest. This is associated with a magnified acute-phase response, peripheral amino acid mobilization, and peripheral lactate production. Thus antecedent TPN may influence the metabolic alterations seen in infection and sepsis via both an exaggerated counter-regulatory hormone response as well as an enhanced systemic and splanchnic production of cytokines.
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PMID:Total parenteral nutrition and bowel rest modify the metabolic response to endotoxin in humans. 250 83

The effect of TNF on nonpulmonary multiple organ damage (MOD) was studied. Since polymorphonuclear leukocytes (PMN) are thought to play an important role in septic or TNF-induced MOD, we investigated both neutrophil sufficient (PMN+) and neutropenic (PMN-) guinea pigs. Sepsis was induced by Escherichia coli administration (2 x 10(9)/kg) or recombinant human TNF (1.4 x 10(6) U/kg) was infused into PMN+ and PMN- guinea pigs. During necropsy, the PMN+/TNF and PMN+/E coli animals exhibited marked damage in the adrenal glands, kidneys and liver as evidenced by hemorrhage, congestion, and PMN sequestration on histopathologic examination. There was also increased tissue albumin accumulation in the adrenal glands, kidneys, spleen, heart, and liver as demonstrated by 125I-labeled albumin determinations. In contrast, the PMN-/TNF group did not reveal histopathologic damage in any organ system and there was no abnormal organ accumulation of 125I-albumin. However, in PMN-/E coli animals, marked histopathologic damage in the adrenal glands and liver was evident. Furthermore, there were marked accumulations of 125I-albumin in the adrenals, heart, kidneys, liver, and spleen. Moreover, the PMN-/E coli guinea pigs had a much greater accumulation (p less than 0.01) of 125I-albumin in the kidneys than any other group including the PMN+/E coli group. Thus, nonpulmonary MOD in guinea pigs is caused by TNF administration and can be prevented by PMN depletion. However, while E coli administration also caused marked nonpulmonary MOD in neutrophil sufficient guinea pigs, equivalent or greater damage was produced in neutropenic animals. This suggests that while TNF-induced MOD may be primarily mediated by PMN, E coli-induced MOD seems to be mediated by more than PMN.
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PMID:Multiple organ damage caused by tumor necrosis factor and prevented by prior neutrophil depletion. 252 93

TNF is a small protein secreted by activated monocytes and macrophages that mediates the in vivo effects of endotoxin. When injected into experimental animals, TNF reproduces the picture of septic or endotoxin shock. In addition, antibodies to TNF protect animals against the deleterious effects of IV injections of either LPS or live bacteria. Specifically, the available evidence suggests that TNF may be necessary for the organ injury and failure seen in sepsis. However, TNF probably is not the final common pathway to shock and tissue injury. Inhibition of cyclooxygenase is protective from the lethal effects of both LPS and TNF infusion, suggesting that prostanoids play an important, and perhaps more proximal role in the generation of tissue injury. In addition, TNF is produced and cleared from the blood-stream within a short period of time after an LPS stimulus, suggesting that TNF sets into motion a chain of events that may be self-perpetuating even in the absence of further TNF stimulus. In the near future, the treatment of sepsis may involve the administration of antibodies both to TNF and to LPS. Cyclooxygenase inhibitors should also begin to play a role in the therapy of sepsis. In the more distant future it is likely that we will be able to manipulate the state of activation of genes that code for TNF to exert some control over its production and secretion. It is perhaps within our grasp to finally reduce the morbidity and mortality of this lethal condition.
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PMID:Role of tumor necrosis factor in sepsis and acute lung injury. 264 25

Inventarising the inflammatory capacities of the three types of inflammatory cells, PMN, macrophages and mast cells, each type seems able to induce a lethal whole body reaction. This whole body inflammation has hitherto largely escaped our attention, as in clinical studies inappropriate methods have been used such as counting peripheral leucocytes, and as monitoring key-mediators (IL-1, TNF, PGE-2, leukotrienes) and key-cells (activated PMN, macrophages and mast cells) hitherto was impossible. Presently a new set of methods is available, allowing a closer look at this whole body inflammation, such as elastase (monitoring PMN activity), neopterin (monitoring macrophage activity) and hopefully clinically practicable methods to monitor cytokines as well as endotoxin-levels. Only after such comprehensive studies have been performed, it might be concluded that--as in the experimental animal--sepsis and MOF may not necessarily be caused by bacteria or their endotoxins, but by an untoward autodestructive and self-sustaining activation of angry leucocytes and mad macrophages.
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PMID:Multiple organ failure: whole body inflammation? 265 70

In a study of serum levels of tumor necrosis factor (TNF alpha) and interleukin-1 beta (IL-1 beta) in patients developing sepsis in the ICU, high TNF alpha levels were found in patients with septic shock. Normal values are 75 +/- 15 pg/ml; in these patients, TNF alpha serum level ranged from 100 to 5000 pg/ml with a mean of 701 +/- 339 pg/ml and a median of 250 pg/ml. There was a correlation between TNF alpha level and sepsis severity score as well as with mortality. In contrast, IL-1 beta serum levels were only slightly increased and were not correlated with severity or mortality.
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PMID:Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans. 279 81

Tumor necrosis factor (TNF; cachectin) has been implicated as a mediator of the toxic manifestations of overwhelming bacterial infection as well as the chronic catabolic state of cancer cachexia. We have examined the acute metabolic and hormonal response after administration of recombinant human TNF in the rat. TNF given by intraperitoneal injection produced dose- and time-related increases in hepatic amino acid uptake, decreases in serum trace metal concentrations, and a pattern of endocrine hormone alterations characteristic of the acute phase response to tissue injury. In vitro zinc transport studies by rat hepatocytes cultured in the presence of TNF alone, or in combination with recombinant human interleukin 1, another mediator of the acute phase response, demonstrated that neither monokine was capable of directly stimulating zinc transport into cells. These findings suggest that TNF may function as an endogenous mediator of the early metabolic response to sepsis and that the trace metal changes induced by TNF in vivo may occur through a secondary mechanism.
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PMID:Hormonal and metabolic response to recombinant human tumor necrosis factor in rat: in vitro and in vivo. 304 39

The effects of sepsis on lipid metabolism may be summarized as follows: The increased plasma catecholamine concentration stimulates adipose tissue FFA release. The increased FFA mobilization and plasma concentration results in an enhanced FFA uptake by the liver which promotes TGFA synthesis and output. Thus, triglyceride appearance rate also can be increased during hypermetabolic sepsis. In severe sepsis, the regulatory signals to increase FFA release from adipose tissue may be counterbalanced by blood flow limitations that inhibit FFA release, possibly due to the inadequate availability of the plasma carrier, albumin. Under such conditions, the arterial FFA concentration may be unchanged or decreased along with similar changes in the rate of peripheral FFA utilization. Triglyceride metabolism can also be altered during septic conditions in which plasma levels of cytokines are very high. Cytokines, notably TNF and IL-1, suppress synthesis of lipoprotein lipase which decreases the rate of TGFA clearance. Thus, hypertriglyceridemia can develop in the absence of elevated plasma FFA levels. The plasma concentration of cytokines necessary to inhibit LPL and how often this form of hypertriglyceridemia occurs in human sepsis are unknown at present. The sequence of events describing the influence of sepsis on carbohydrate metabolism is postulated to be the following: The presence of bacteria, or their products (eg, endotoxin) either directly or indirectly (via stimulating mononuclear phagocytes to release cytokines) activate the immune tissues. Glucose utilization by these tissues, which are predominantly glycolytic, is thereby stimulated resulting in increased lactate production. At the same time, glucose uptake by skeletal muscle and lactate release are also elevated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in lipid and carbohydrate metabolism in sepsis. 306 39

Glucose utilization of different tissues was investigated in vivo by the 2-deoxyglucose tracer technique. After infusion of a non-lethal dose of recombinant human TNF-alpha (150 micrograms/kg) to rats, glucose utilization was increased by 80-100% in spleen, liver, kidney, by 60% in skin and by 30-40% in lung and ileum. The largest increase (150%) was observed in the diaphragm. There was no significant change in glucose utilization by skeletal muscles, testis and brain. These data show that TNF exerts metabolic effects on macrophage-rich tissues, and suggest that enhanced secretion of TNF may be one of the important factors in eliciting the metabolic changes in sepsis and endotoxicosis.
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PMID:Tumor necrosis factor increases in vivo glucose utilization of macrophage-rich tissues. 368 7


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