Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mice were subjected to sepsis by cecal ligation and puncture to determine whether macrophages from endotoxin-tolerant C3H/HeJ mice are also activated systemically to release inflammatory monokines associated with septic mortality. Blood levels of both tumor necrosis factor and interleukin 6 were significantly elevated during the first 1 to 4 hours of sepsis as compared with sham controls. Peritoneal macrophages from septic mice exhibited a marked spontaneous release of interleukin 1, interleukin 6, and tumor necrosis factor at 1 hour. However, the addition of endotoxin to macrophage cultures taken from septic mice had no further stimulatory effect. Sham controls alternatively showed no significant innate monokine release, but their macrophages did release increased monokine numbers in response to endotoxin. These results indicate that the spontaneous macrophage release of these monokines is comparable with that previously observed in endotoxin-sensitive mice, suggesting a common mechanism by which macrophages are primed by traumatic injury by an agent other than endotoxin to release monokines during sepsis. Thus, the administration of agents that decrease or prevent the deleterious effects of systemic inflammatory mediators during sepsis could be useful adjuvants in those clinical situations where the bacterial origin is unknown.
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PMID:Does endotoxin tolerance prevent the release of inflammatory monokines (interleukin 1, interleukin 6, or tumor necrosis factor) during sepsis? 154 97

The level of tumor necrosis factor alpha (TNF alpha), a monokine implicated in mediating septic shock, is elevated in the blood of some patients with sepsis. Monocytes from 11 trauma patients and 11 burn patients were suboptimally stimulated with interferon gamma and muramyl dipeptide, an analogue of bacterial wall products. The patients with sepsis showed significantly greater total TNF alpha levels (secreted in combination with cell-associated) 3 days before septic episodes, as compared with normal controls (32.38 to 2231.76 ng/10(6) monocytes per milliliter, median = 121.03 ng/10(6) monocytes per milliliter; normal control: 0.00 to 18.20 ng/10(6) monocytes per milliliter, median = 5.93 ng/10(6) monocytes per milliliter). Increases in patients' total monocyte TNF alpha levels greater than 30 ng/10(6) monocytes per milliliter correlated with septic episodes. In patients with sepsis, the total monocyte TNF alpha levels were increased despite a concomitant increase in their prostaglandin E2 levels in both stimulated (interferon gamma plus muramyl dipeptide) and unstimulated in vitro assays (9 patients: stimulated prostaglandin E2 range, 30.1 to 123.6 ng/10(6) monocytes per milliliter). Massively elevated monocyte TNF alpha and prostaglandin E2 production occurred simultaneously in patients with sepsis.
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PMID:Elevated tumor necrosis factor alpha production concomitant to elevated prostaglandin E2 production by trauma patients' monocytes. 210 44

The objective of this study was to analyze monokine production by peripheral blood mononuclear cells from patients with alcoholic cirrhosis. The capacity of peripheral blood mononuclear cells and purified monocytes from these patients to produce tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 was investigated. Spontaneous production of tumor necrosis factor alpha, interleukin 6 and interleukin 1 beta was similar in cirrhotic and healthy subjects, but serum levels of interleukin 6 (less than 2 U/ml vs. 9.5 +/- 3 U/ml) and tumor necrosis factor alpha (3.1 +/- 1.2 pg/ml vs. 12.0 +/- 1.2 pg/ml) were significantly higher in cirrhotic patients. However, peripheral blood mononuclear cells or purified monocytes from patients with alcoholic liver cirrhosis, stimulated in vitro with Escherichia coli lipopolysaccharide, displayed a marked increase of tumor necrosis factor alpha, interleukin 1 beta and interleukin 6 secretions compared with healthy controls. A striking feature of this overproduction was its reversibility as assessed by allowing cells to rest in vitro without lipopolysaccharide for 1 to 7 days before stimulation. In such conditions, tumor necrosis factor alpha and interleukin 6 secretions declined to levels present in healthy subjects in whom production remained stable, whereas interleukin 1 beta secretion markedly decreased in both groups to the point where no difference could be seen. This reversible oversecretion of cytokines after lipopolysaccharide stimulation, along with the lack of abnormality of spontaneous cytokine secretion, suggests that monocytes in these patients may have undergone an in vivo activation process analogous to a priming phenomenon. The in vitro activation with lipopolysaccharide may represent the correlate of in vivo endotoxemia observed during acute events such as sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Excessive in vitro bacterial lipopolysaccharide-induced production of monokines in cirrhosis. 218 15

The insulin stimulatory effect of 7 mM glucose on isolated perifused rat islets is dramatically potentiated by the monokine interleukin 1 (IL-1). At levels (10(-10) -10(-8) M) noted in vivo during sepsis, it reversibly amplifies peak second phase insulin release to the hexose. At 2.75 mM glucose, however, IL-1 has no effect on insulin secretion. IL-1 also potentiates glyceraldehyde (2 mM)- and alpha-ketoisocaproate (5 mM)-induced insulin secretion. In islets whose phosphoinositides were prelabeled with myo-[2-3H]inositol, 2.0-5.0 nM IL-1 increases the efflux of [3H]inositol from subsequently perifused islets, the parallel accumulation of labeled inositol phosphates, and insulin secretion in the simultaneous presence of 7 mM glucose but not 2.75 mM glucose. In support of these in vitro observations, the in vivo infusion of IL-1 (40 micrograms/kg body wt) elevated circulating plasma insulin levels two-to fourfold. These results establish IL-1 as a potent, readily reversible, glucose-dependent modulator of stimulated insulin secretion and further suggest that its positive impact on insulin release is mediated, at least in part, by phosphoinositide-derived second messenger molecules. IL-1-induced insulin secretion may participate in the multiple metabolic and immunologic adaptations occurring during sepsis.
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PMID:Interleukin 1 is a potent stimulator of islet insulin secretion and phosphoinositide hydrolysis. 253 31

Multiple organ failure continues to be the primary cause of death after trauma and sepsis. This clinical syndrome represents the transition from a hypermetabolic response to injury to a syndrome of progressive organ failures and death. Risk factors include: perfusion deficits, persistent foci of dead or injured tissue, an uncontrolled focus of infection, the presence of the respiratory distress syndrome, persistent hypermetabolism, and preexisting fibrotic liver disease. Once initiated, most treatment modalities for the organ failure syndrome become progressively ineffective including: ventilation, antibiotics, nutrition, and surgery. The best treatment remains prevention and rapid control of risk factors including restoration of oxygen transport and aggressive nutrition support. There seems to be no treatment "magic bullet" either experimentally or clinically once the syndrome has occurred. The metabolic response to injury involves alterations in physiology and in the metabolism of carbohydrate, fat and amino acids. These changes seem to reflect the modulation of the end-organs by the mediator systems activated in response to the stress stimuli. The transition from hypermetabolism to organ failure appears to reflect the clinical appearance of liver failure. It is hypothesized that this liver failure may represent a state of regulatory dysfunction induced in large part by the activated hepatic macrophage, the Kupffer cell. The activation of these macrophages is hypothesized to represent the final stage of a series of stimulating events, eg. hypoxia, endotoxin, bacteria, and gut translocated toxins. The precise monokine(s) responsible are not yet completely characterized, although Interleukin-1 (IL-1) and tumor necrosis factor (TNF) appear to be involved as do prostaglandins (Pg) such as PgE2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of monokines in altering hepatic metabolism in sepsis. 264 13

Multiple system organ failure (MSOF) is a progressive dysfunction of vital organs that may develop in clinical settings such as sepsis or multiple trauma. One component of this syndrome is cholestasis and impaired liver function. The mechanism(s) for this liver failure (and the failure of other organs) remains obscure. Macrophages and Kupffer cells have been shown to secrete cytokines such as interleukin-1 and tumor necrosis factor. These cytokines mediate many aspects of the acute phase response, and they also can produce cellular injury. The purpose of this study was to evaluate the effects of a semipurified murine monokine preparation having interleukin-1 activity on bile flow in the rat isolated perfused liver (IPL). The monokine preparation produced a significant reduction of bile flow in the IPL system. The effect could not be explained by a venoocclusive phenomenon or residual endotoxin in the monokine preparation. We conclude that a semipurified monokine preparation having interleukin-1 but not tumor necrosis activity produced a significant depression of bile flow in the IPL, and we suggest that macrophage secretory product(s) may be responsible for the cholestasis in MSOF.
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PMID:Monokine depression of bile flow in the isolated perfused rat liver. 277 Feb 82

Sepsis and endotoxaemia are common in fulminant hepatic failure (FHF) and may contribute to multisystem disease in such patients. Tumour necrosis factor (TNF) is a probable mediator of endotoxic shock and infusion of this monokine into animals causes multi-organ failure that shares features with FHF. In patients with FHF, TNF production was increased and correlated closely with activity of interleukin-1, another cytokine that is released by monocytes/macrophages in response to infection and endotoxin and is produced in increased quantities in FHF. Interleukin-2 activity was impaired in FHF and correlated negatively with TNF production.
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PMID:Enhanced tumour necrosis factor and interleukin-1 in fulminant hepatic failure. 289

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

Tumor necrosis factor alpha (TNF), a monokine produced by mononuclear cells in response to bacterial endotoxin (LPS), creates a syndrome similar to septic shock in animal models. To study whether TNF could induce acute lung injury similar to that seen in gram-negative sepsis, we injected recombinant human TNF (rHuTNF alpha) into guinea pigs and monitored arterial blood gases, leukocyte counts, and left atrial (Pla), pulmonary artery (Ppa), and mean arterial pressures (MAP) serially for 8 h. Pulmonary histopathology was assessed microscopically, and cell counts and 125I-labeled albumin (125I-albumin) in bronchoalveolar lavage (BAL) fluid and lung wet/dry weight ratios were determined. Five groups of animals were studied; the 2 TNF groups received high (1.4 X 10(6) U/kg) or low (1.0 X 10(6) U/kg) doses of rHuTNF alpha, the sepsis group received 2 X 10(9) Escherichia coli/kg intravenously, and the control group received saline. An LPS control group receiving 40 ng/kg E. coli LPS was also included because the rHuTNF alpha contained a small amount of LPS as a contaminant. Pulmonary permeability was assessed by studying the Pla and the BAL fluid/plasma 125I-albumin ratio (permeability index). The permeability index was significantly increased in the high-dose TNF (0.0408 +/- 0.0041, p less than 0.05) and sepsis groups (0.0466 +/- 0.0068, p less than 0.01) relative to controls (0.0215 +/- 0.0028). The wet/dry lung weight ratios were also significantly increased in the high-dose TNF (6.07 +/- 0.29, p less than 0.05) and sepsis groups (6.22 +/- 0.30, p less than 0.05) relative to the control group (5.18 +/- 0.20).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor causes increased pulmonary permeability and edema. Comparison to septic acute lung injury. 305 59

Multiple organ failure continues as the main cause of death after burns, trauma and sepsis. This clinical syndrome represents the transition from a hypermetabolic response to injury to a setting of clinical organ failures and death. Risk factors include: perfusion deficits, persistent foci of dead or injured tissue, an uncontrolled focus of infection, the presence of the respiratory distress syndrome, persistent hypermetabolism, and preexisting fibrotic liver disease. Once in the organ failure syndrome, most treatment modalities become progressively ineffective, including: ventilation, antibiotics, nutrition, and surgery. The best treatment remains prevention with rapid control of the source and restoration of oxygen transport. The response to injury involves alterations in physiology and in the metabolism of carbohydrate, fat and amino acids. These changes seem to reflect the modulation of the end-organs by the mediator systems activated in response to the stress stimulus. The transition from hypermetabolism to organ failure appears to reflect the clinical appearance of liver failure. It is currently hypothesized that this liver failure represents a state of regulatory dysfunction induced by the activated hepatic macrophage, the Kupffer cell. This same process may also influence metabolic failure in other organs where this cell-cell regulation can occur, e.g. kidney, lung. The activation of these macrophages is hypothesized to represent the final stage of a series of continuous stimulating events, eg. hypoxia, endotoxin, bacteria, and gut translocated toxins. The precise monokine(s) responsible are not yet completely characterized. Treatment consists of the modalities outlined above and the employment of aggressive metabolic (nutritional) support.
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PMID:Hypermetabolism/organ failure: the role of the activated macrophage as a metabolic regulator. 328 26


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