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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple organ failure (MOF) is presently recognized as the most severe, and often lethal, complication after multiple trauma. Causal factors and pathomechanisms remain unclear, however. Generalized inflammatory cell tissue injury with a subsequent increase in permeability in all organs has been suggested. For this reason, 38 polytraumatized patients were examined in a prospective study. Organ function was analyzed, and specific clinical and histological studies were performed to check for generalized cell tissue damage and increased respiratory permeability. In all organs we found signs of tissue damage immediately after trauma. Disturbances of organ function were seen consistently, starting precisely from day 4. It was not possible to confirm an influence of blunt organ trauma on organ function during follow-up. The severity of injury (especially intrathoracic and intraabdominal) and massive bleeding increases the risk of MOF. MOF was not always associated with the onset of sepsis, and no temporal dependence could be shown. Histological studies demonstrated an inflammatory change in organ tissues, which is probably the result of toxic substances (endotoxin, TNF, oxygen radicals, proteases and eicanosoids) released into the blood circulation after trauma. Insufficient neutralization of these toxic metabolites leads to generalized permeability damage and consequently to progressive organ failure. Therefore, even with optimized initial treatment of multiple trauma patients, MOV and mortality can only be reduced with a causal approach to therapy.
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PMID:[Multiple organ failure. Reflection of generalized cell damage of all organs following severe trauma]. 195 74

The role of tumor necrosis factor-alpha (TNF alpha) in the lethal consequences of intravascular lipopolysaccharide (LPS) or Escherichia coli sepsis was compared with that in bacterial peritonitis. Intravenous administration of E. coli LPS or E. coli (live or dead) resulted in large transient increases in serum TNF alpha levels, peaking at 90 min at 10,000-30,000 units/ml. In contrast, the serum TNF alpha response following the induction of bacterial peritonitis was substantially less, peaking at 200-500 units/ml. Sterile peritonitis (essentially nonlethal) and bacterial peritonitis (greater than 60% lethal) elevated TNF alpha levels to 1000-2000 units/lavage within the peritoneal cavity 2 h after challenge. Passive immunization with neutralizing goat anti-TNF alpha IgG improved survival from 8% to 75% in rats administered LPS intravenously but was completely ineffective in protecting rats from lethal E. coli peritonitis. Thus significant differences exist in the role TNF alpha plays in systemic intravascular models of sepsis and bacterial peritonitis.
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PMID:Divergent efficacy of antibody to tumor necrosis factor-alpha in intravascular and peritonitis models of sepsis. 198 80

The purpose of the study was to evaluate the role of tumor necrosis factor alpha (TNF alpha) in the pathogenesis of acute lung injury in critically ill patients. An immunoradiometric assay with an upper normal limit of 9 pg/ml was used to measure plasma TNF alpha levels (pl-TNF alpha) in 34 patients with adult respiratory distress syndrome (ARDS) and in 16 patients in whom, despite the presence of risk factors, ARDS did not develop. Pl-TNF alpha was elevated in 76% of the patients with ARDS (71 +/- 104 pg/ml) and in 48% of the at-risk patients (47 +/- 73 pg/ml); the difference between the two groups was not statistically significant. In 13 patients studied serially from the onset (Day 0) to the fifth day of ARDS, the peak pl-TNF alpha occurred later than Day 0 in seven subjects. Although the highest pl-TNF alpha levels were found in septic patients, moderately elevated values were also observed in 56% of nonseptic subjects. We conclude that plasma TNF alpha level is not a marker of ARDS but rather of shock and sepsis. These results do not exclude a pathogenic role of TNF alpha in acute lung injury since this cytokine could be produced and exert its effects within the lungs. The large incidence of abnormally high could be produced and exert its effects within the lungs. The large incidence of abnormally high plasma TNF alpha levels raises important questions on the role of this toxic cytokine in other disorders occurring in critically ill patients.
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PMID:Plasma levels of tumor necrosis factor in the adult respiratory distress syndrome. 200 Oct 71

Interleukin 8 (IL-8), a potent activator of neutrophils, may be important in the early host response to serious Gram-negative infections. IL-8 was measured with other acute phase cytokines (tumor necrosis factor alpha [TNF-alpha], IL-6 and IL-1 beta) in 25 normal humans randomized to receive either intravenous endotoxin alone or endotoxin after oral administration of ibuprofen or pentoxifylline, agents that alter some of the inflammatory responses induced by endotoxin in vitro. TNF immunoreactivity was maximum at 1.5 h, and total TNF (area under the curve) was 4.2- and 4.5-fold greater in subjects given endotoxin/ibuprofen compared to subjects given endotoxin alone (p = 0.026) or endotoxin/pentoxifylline (p = 0.004), respectively. IL-6 levels were maximum at 2-3 h and did not differ among the three groups. No IL-1 beta was detected in any subject. IL-8 levels peaked at 2 h in subjects given either endotoxin alone or endotoxin/pentoxifylline, falling towards baseline by 5 h. Subjects given endotoxin/ibuprofen had a more sustained rise in IL-8 with peak levels 2.8- and 2.5-fold higher at 3 h compared to endotoxin alone (p = 0.048) or endotoxin/pentoxifylline (p = 0.023), respectively. Differences in total IL-8 release among groups approached statistical significance (ANOVA, p = 0.07). This trend reflected the increased release of IL-8 by the subjects receiving ibuprofen compared to pentoxifylline (1.9-fold higher; p = 0.024). This suggests that cyclooxygenase products may provide important negative feedback loops for cytokine production in vivo. Increases in circulating IL-8 are part of the acute inflammatory response of humans to endotoxin. Altered cytokine responses caused by antiinflammatory therapy may have important implications for both host defense and injury during septicemia.
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PMID:Detection of interleukin 8 and tumor necrosis factor in normal humans after intravenous endotoxin: the effect of antiinflammatory agents. 200 51

It is currently hypothesized that the mechanisms of cancer cachexia involve the host's production of inflammatory cytokines, which in turn orchestrate a series of complex interrelated steps that ultimately lead to a chronic state of wasting, malnourishment, and death (see Fig. 1). The metabolic changes seen in the tumor-bearing host are similar, but not identical, to those seen in sepsis and inflammation and appear to result from a generalized response of the host to the stimulus of invasion--the tumor. Although there are likely to be several humoral factors, of either host or tumor origin (see Fig. 1), involved in cancer cachexia, recombinant DNA methodology has provided sufficient amounts of only a few cytokines to enable careful investigation of their cachectic potential. TNF/cachectin has been most extensively studied and appears to play a clear role, because administration of low-dose continuous or escalating doses simulates changes associated with cancer cachexia. In addition, these cachectic changes have been blocked by a specific antisera. IL-1, IL-6, and interferon-gamma all have potential as mediators of cancer cachexia and more work is clearly indicated. It is possible that, given our current understanding of the mechanisms of cancer cachexia, it can be theorized that TNF, which causes many of the manifestations of cancer cachexia, and IL-1 are released by macrophages in response to tumor (see Fig. 1). Interferon-gamma appears to potentiate these effects and may also be necessary for the complete syndrome of cancer cachexia. IL-6 probably is released as another mediator, principally mediating the acute phase response seen in cancer cachexia. Other factors are certain to be involved. Further study into the mechanisms and possible treatment of cancer cachexia is needed, because a large proportion of cancer patients who are incurable by current therapies continue to suffer from this lethal wasting diathesis. Furthermore, specific strategies to reverse the cachectic changes associated with cancer will likely improve antitumor treatment.
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PMID:Mechanisms of cancer cachexia. 202 66

Recent studies in alcoholic hepatitis have proposed a role for the cytokine tumour necrosis factor-alpha (TNF-alpha) a mediator of endotoxic shock in sepsis. In this study plasma levels of the closely related cytokine interleukin-6 (IL-6) were assayed in 96 samples from 58 patients with severe alcoholic hepatitis, and 69 patients in control groups (21 normal, 10 alcoholic without liver disease, 10 inactive alcoholic cirrhosis, 18 chronic liver disease, 10 chronic renal failure). Plasma IL-6 levels were markedly elevated in patients with alcoholic hepatitis when compared with all control groups (P less than 0.001). IL-6 levels were higher in patients who died (P = 0.04) and correlated with the features of severe disease including: increased grade of encephalopathy, increased neutrophil count, increased prothrombin ratio, hypotension, increased serum creatinine and increased serum bilirubin. Surprisingly, no correlation was found between levels of plasma IL-6 and plasma TNF-alpha or endotoxin, or the presence of infection; an inverse correlation was found between plasma IL-6 and serum globulins. These findings provide further evidence that the IL-6/TNF cytokine system is activated in severe alcoholic hepatitis and may mediate hepatic or extra-hepatic tissue damage.
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PMID:Elevated plasma interleukin-6 and increased severity and mortality in alcoholic hepatitis. 204 24

Recent experiments have demonstrated that TNF plays an important role in the pathogenesis of septic shock. To confirm the involvement of TNF in human septic shock, serum TNF levels were measured in 10 adult patients admitted to the intensive care unit for sepsis with or without shock. Septic shock was corroborated by hemodynamic data (right catheterization, measurement of cardiac output by thermodilution). For TNF measurement, venous blood samples were withdrawn, as soon as possible after the onset of sepsis, into a pyrogen--free tube. Serum TNF levels were determined using a radioimmunoenzymatic assay (IRE Medgenix). During septic shock (n = 7), TNF levels were significantly higher (m = 354 +/- 131 pg/ml) than during sepsis without shock (n = 8; m = 145 +/- 35 pg/ml) (p less than 0.0005). TNF levels were also significantly higher in non-survivors (m = 392 +/- 111 pg/ml) than in survivors (m = 167 +/- 81 pg/ml) (p less than 0.0005). The value of 250 pg/ml seems to be critical: no patient without shock had TNF levels above 250 and all the patients who died early during the first 24 h) had TNF levels above 250. The TNF level is negatively correlated with the platelet count (r = -0.70; p less than 0.05). These data favor a pathophysiological for TNF in human sepsis and septic shock.
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PMID:[TNF and sepsis]. 206 71

Tumor necrosis factor-alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha) are pluripotent cytokines mediating the host response to sepsis, injury, and cancer. Animals can be protected from the lethal effects of TNF alpha by repeated administration of sublethal doses, but the mechanism of this effect is not known. Human foreskin fibroblasts (FS4 cells), which rapidly elaborate interleukin-6 (IL-6) when stimulated with TNF alpha or IL-1 alpha, were grown in culture as confluent monolayers and their secretion of IL-6 was quantitated using the murine B9-hybridoma bioassay against an external reference of human recombinant IL-6 (Genetics Institute). When FS4 cells were incubated with human recombinant TNF alpha (50 ng/ml; Cetus) or recombinant IL-1 alpha (30 pg/ml; Genzyme) a rapid increase in IL-6 production was measured over control, rising to IL-6 levels of 71.7 +/- 5.9 units/ml with TNF alpha and 54.0 +/- 1.2 units/ml with IL-1 alpha after 7.5 hr incubation. FS4 cells which were exposed to cytokine, rinsed, and then reexposed to cytokine 24 hr later produced significantly less IL-6 [38.1 +/- 2.8 units/ml with second exposure to TNF alpha (P less than 0.05), and 18.3 +/- 1.9 units/ml with second exposure to IL-1 alpha (P less than 0.01)]. Successive daily exposure to TNF alpha or IL-1 alpha caused a further stepwise diminution of IL-6 secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased IL-6 secretion by fibroblasts following repeated doses of TNF alpha or IL-1 alpha: post-transcriptional gene regulation. 206 55

Although antibiotics have reduced mortality, the most recent clinical trials in sepsis and meningitis have been directed at the host inflammatory response in an attempt to improve outcome. Endotoxin, cell wall constituents and toxins are potent inducers of small molecular weight proteins (cytokines) from a variety of host cells. Several lines of investigation have implicated tumor necrosis factor-alpha (TNF-alpha) as a cytokine mediator of sepsis and septic shock. A recent study has been able to measure plasma TNF-alpha concentrations in patients with meningococcemia and demonstrated a correlation with prognostic groups related to mortality. Therefore, TNF-alpha, probably through its effects on other mediators, has an effect in sepsis. New speculation regarding morbidity in bacterial meningitis focuses on cytokine activity in the central nervous system. Cerebrospinal fluid (CSF) from experimental animals with meningitis contains increased amounts of interleukin-1 beta (IL-1 beta) and TNF alpha. These IL-1 beta levels correlated directly with duration of fever and neurological sequelae. Children with Haemophilus influenzae, type b meningitis treated with dexamethasone had significantly reduced levels of CSF IL-1 beta compared to placebo-treated controls.
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PMID:The immunology of sepsis and meningitis--cytokine biology. 209 Dec 57

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


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