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

Hemorrhagic shock causes severe depression of macrophage functions and is associated with increased susceptibility to sepsis. Because hemorrhagic shock and resuscitation encompasses several pathophysiological conditions, such as hypotension, low-flow conditions, hypoxia, and reperfusion injury, it remains unknown whether severe hypotension in the absence of blood loss has any adverse effects on macrophage functions. To study this, systemic arterial hypotension was induced in C3H/HeN mice for 15 min by intravenous infusion of sodium nitroprusside or ATP-MgCl2. Peritoneal macrophages (PM) was harvested 20 h later with lavage. Antigen presentation was measured by coculturing PM with the D10.G4.1 Th cell clone. Tumor necrosis factor (TNF), interleukin (IL)-6, IL-1, and prostaglandin (PG) E2 levels in supernatants of PM stimulated with lipopolysaccharide were measured with bioassays or radioimmunoassay. Systemic arterial hypotension resulted in a significant decrease of PM capacity to present antigen. Although the release of TNF, IL-6, and IL-1 by PM was unaltered after hypotension, PGE2 release by PM was significantly elevated compared with the control group. These data indicate that chemically induced systemic arterial hypotension without blood loss leads to a depression of antigen presentation, which may be caused by elevated release of the immunosuppressive eicosanoid PGE2.
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PMID:Chemically induced hypotension increases PGE2 release and depresses macrophage antigen presentation. 847 8

Tumor necrosis factor-alpha, IL-1 beta, and IL-6 are thought to be involved in the pathogenesis of sepsis with gram-negative bacteria. We studied these cytokines during neonatal sepsis with mainly gram-positive bacteria. Ten newborns with clinical sepsis and 22 healthy controls were enrolled in the study. TNF alpha plasma levels proved to be increased in the newborns with sepsis up to 560 +/- 234 pg/mL (ng/L) versus 36 +/- 4 pg/mL (ng/L) in the control group (p < 0.005), whereas IL-6 plasma levels in newborns with sepsis were 79.700 +/- 37.500 pg/mL (ng/L) versus 55 +/- 28 pg/mL (ng/L) in the control group (p < 0.01). The IL-1 beta plasma levels were only slightly elevated in the group newborns with sepsis [up to 18 +/- 5 pg/mL (ng/L) versus 7 +/- 1 pg/mL (ng/L) in the control group (p < 0.01)]. After the start of therapy with antibiotics, both TNF alpha and IL-6 plasma levels decreased concomitantly with the improvement of the clinical situation within 2 d. These data confirm the abundant presence of TNF alpha and IL-6 during neonatal sepsis, whereas IL-1 beta appeared to be present in small amounts only. Nevertheless, the IL-1 beta but not the TNF alpha plasma level appeared to correlate inversely with the decrease in diastolic tension as standardized according to birth weight (R = 0.66, p = 0.04). TNF alpha, IL-1 beta, and IL-6 were not correlated with any febrile response in the group with sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 plasma levels in neonatal sepsis. 847 19

Although recent studies have shown that gut absorptive function is significantly depressed even in the early hyperdynamic phase of sepsis, the mechanism responsible for this is unknown. Tumor necrosis factor (TNF-alpha) is a potent mediator of shock resulting in a marked inflammatory response leading to mucosal erosions of the gut and multiple organ failure. Although TNF is elevated in early sepsis, it remains unknown whether TNF plays any role in the depression of gut absorptive function under these conditions. To study this, we used the 1 hr D-xylose absorption test. C3H/HeN mice (n = 12) were lightly anesthetized, and a femoral artery and the portal vein were cannulated. After recovery from anesthesia, 125 micrograms recombinant murine TNF-alpha (rMuTNF-alpha)/kg body weight was given via the tail vein to one group of animals, while another group received an equivalent volume of saline (sham). One hour later, D-xylose was given orally. The systemic blood pressure was recorded 1 hr thereafter and D-xylose concentration in a sample of portal blood was determined colorimetrically. Results show that, while the systemic pressure was elevated 2 hr after administration of rMuTNF-alpha, D-xylose absorption was severely depressed. Thus the depressed gut absorptive function seen in the early stage of sepsis may be mediated directly or indirectly by TNF-alpha.
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PMID:Tumor necrosis factor depresses gut absorptive function. 848 19

Candidemia in humans is often associated with an endotoxic shock-like syndrome, comparable to gram-negative sepsis. Tumor necrosis factor-alpha (TNF alpha) has been implicated as a mediator in the endotoxic shock syndrome. The possible role of TNF alpha causing early deaths was explored in a murine model of acute infection with Candida albicans. In vitro data from three mouse strains (BALB/c, C3H/HeJ, and C3H/HeN) and in vivo data from BALB/c mice were obtained. Peritoneal macrophages from all three strains produced TNF alpha in vitro when stimulated with C. albicans. After intravenous infection with 10(8) cfu of C. albicans, mice died within 12 h. TNF concentrations in sera from these mice were significantly greater than in controls. Pretreatment of BALB/c mice with anti-murine TNF alpha did not alter mortality of C. albicans-infected mice, but pretreatment with murine TNF alpha reduced mortality. Therefore, in contrast to what was anticipated, TNF alpha may serve a protective role in murine candidiasis.
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PMID:Induction of tumor necrosis factor-alpha in murine Candida albicans infection. 848 50

Tumor necrosis factor (TNF) has a pivotal role in the pathogenesis of sepsis and septic shock. Suppression of its biosynthesis might therefore be one of the strategies in the treatment of sepsis. When peripheral white blood cells were stimulated with either E. coli lipopolysaccharide (LPS) or Staphylococcus aureus, pentoxifiline (PTX) inhibited TNF production. In contrast, only a moderate inhibitory effect was observed on the induction of interleukin 6 (IL-6). PTX inhibited not only the TNF production of monocytes, but also the TNF secretion of both granulocytes and unseparated whole blood. The in vitro TNF and IL-6 producing capacities were higher in septic patients (n = 31) than in healthy blood donors (n = 15). Administration of PTX (400 mg/day) to 20 of the septic patients resulted in TNF production similar to that found in healthy controls. It also subsequently led to an improvement of the clinical status classified by the APACHE II score. The soluble intercellular adhesion molecule-1 (sICAM-1) level was significantly higher in the sera of septic patients before PTX treatment (800-1200 ng/ml) than in normal individuals (50-150 ng/ml), but it decreased following PTX therapy. Cytofluorometric analysis revealed that the expression of ICAM-1 on stimulated mononuclear cells was inhibited by PTX. It is presumed that the suppressive effect of pentoxifylline on TNF production may be of clinical importance, improving the therapeutic strategies in septic syndrome.
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PMID:Inhibition of tumor necrosis factor production and ICAM-1 expression by pentoxifylline: beneficial effects in sepsis syndrome. 857 38

Sepsis is a leading cause of death following major trauma and complicated abdominal surgery. Tumor necrosis factor-alpha (TNF) is believed to be a central mediator in the inflammatory response syndrome. Numerous methods of blunting the TNF response in sepsis have been attempted with suggestion of increased survival and decreased organ injury. Thalidomide, shown in vitro to selectively inhibit TNF production, has been used clinically in states of chronic TNF elevation with encouraging results. In this study, we examined the effect of thalidomide administration in a rat model of acute septic shock. Femoral artery cannulation was performed and baseline TNF measured. Dose response was determined by giving varying doses of thalidomide by gavage. Rats were injected intraarterially with endotoxin and serial samples drawn. TNF was measured by ELISA. For survival, thalidomide was given by gavage and endotoxin injected intraperitoneally. Serum TNF elevation occurred after endotoxin injection with peak levels at 90 min. Thalidomide treated rats had lower TNF levels at all time points (P = <0.01 at 90 and 120 min), with the inhibition being dose dependent. Survival in treated rats exceeded that of untreated rats (53% vs 19%, P = <0.05) at 48 and 72 hr. In conclusion, we found that thalidomide administration leads to increased survival following acute endotoxemia, which may be due to the observed TNF inhibition.
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PMID:Thalidomide inhibits TNF response and increases survival following endotoxin injection in rats. 866 Nov 87

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) are major mediators of sepsis and multiple organ failure. Serum-mediated macrophage activation requires lipopolysaccharide (LPS) and its serum binding protein, lipopolysaccharide binding protein as a ligand for the receptor CD14. This study was designed to determine whether cytokines participate in regulation of serum-mediated LPS activation. Rat macrophages were stimulated with LPS with and-without TNF-alpha or IL-1 beta and activation was determined by detection of TNF-alpha by specific enzyme-linked immunosorbent assay or TNF-alpha mRNA by Northern blot analysis. The addition of TNF-alpha but not IL-1 beta, in the presence of serum, leads to potentiation of macrophage activation after LPS stimulation. This effect could be specifically inhibited by neutralization of LPS with polymyxin B or an antibody against TNF-alpha. This study shows that LPS and TNF-alpha synergize to potentiate serum-mediated macrophage activation. These results demonstrate another element of the control mechanism of cytokine secretion following macrophage activation in sepsis.
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PMID:Lipopolysaccharide and tumor necrosis factor-alpha synergy potentiate serum-dependent responses of rat macrophages. 879 55

Endotoxemia initiates a cytokine response that is thought to mediate the syndromes of sepsis and multiple organ failure. This study measured cytokine levels in the blood and airways of rats at critical time points during the development of lung injury induced by chronic endotoxin (LPS) infusion in the rat. Tumor necrosis factor-alpha (TNF), interleukin-1-beta (IL-1), and interleukin-6 (IL-6) were measured in the blood and bronchoalveolar lavage fluid (BALF) of endotoxemic and control animals. BALF was also studied for the percentage of neutrophil (PMN) count and chemotactic activity. Lung histology was determined at 72 h following infusion of LPS. Chronic endotoxemia of > or = 48 h but not < or = 24 h resulted in severe acute lung injury (ALI). Circulating levels of TNF and IL-1 were only transiently elevated, whereas IL-6 remained elevated in the endotoxemic rats. TNF, IL-1, and IL-6 levels in BALF were only transiently elevated. Chemotactic activity, levels of cytokine-induced neutrophil chemoattractant (CINC), and the percentage of PMN counts in BALF all increased significantly by 36 h. Other potential chemoattractants; leukotriene B4 and transforming growth factor-beta were not elevated in BALF. In conclusion, severe ALI requires a minimum of 48 h LPS infusion in this model and is associated with high levels of circulating IL-6, increased CINC activity, and an increased percentage of PMN count in BALF. Local inflammatory events may be as important as the systemic cytokine milieu in mediating ALI. The signal for these local events does not appear to depend solely on the transient elevations of circulating TNF and IL-1 at the onset of endotoxemia, although sustained high levels of IL-6 may be important.
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PMID:Acute lung injury in endotoxemic rats is associated with sustained circulating IL-6 levels and intrapulmonary CINC activity and neutrophil recruitment--role of circulating TNF-alpha and IL-beta? 882 83

Tumor necrosis factor (TNF) is recognized as a central mediator of sepsis, septic shock, and multiple organ failure. These host reactions are associated with increased TNF levels in circulation, presumably due to increased TNF production. A previously described nucleotide variation at position -308 in the promoter region of the human TNF gene was shown to be associated with the clinical outcome of malaria. In this study we addressed the relevance of the -308 polymorphism for expression of the human TNF gene in response to bacterial endo- toxin in vivo and in vitro. First, we typed 80 patients suffering from severe sepsis and 153 healthy individuals and found no association of the -308 variation with incidence of the disease. In contrast, the NcoI marker in the closely linked lymphotoxin-alpha (LT-alpha) gene showed association with survivaL This discrepancy can be explained by the linkage of the TNFB2(NcoI) allele to the common TNF1 (-308) allele. Second, we generated reporter gene constructs with the promoter deletions and with both -308 variation in the context of the extended human TNF promoter region. Although such constructs were highly inducible by lipopolysaccharide (LPS) in transient transfections into a macrophage cell line, the -308 variation had no significant effect on transcription, consistent with the promoter deletion study. We conclude that the functional consequence of the -308 polymorphism may be unrelated to transcriptional response of the TNF gene to bacterial endotoxin.
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PMID:-308 tumor necrosis factor (TNF) polymorphism is not associated with survival in severe sepsis and is unrelated to lipopolysaccharide inducibility of the human TNF promoter. 883 66

Tumor necrosis factor-alpha (TNF) is believed to play an important role in mediating many of the pathophysiologic changes accompanying bacterial sepsis. In order to characterize the cardiopulmonary responses to TNF in a young animal model and to determine to what extent these changes were secondary to cyclooxygenase byproducts, three groups of mechanically ventilated piglets received an infusion of either TNF, indomethacin followed by TNF (Indo+TNF) or neither (control). Compared to controls at 120 min, TNF resulted in the following changes beginning 30-60 min after the infusion began: mean pulmonary artery pressure (Ppa) increased from 1.7 +/- 0.3 to 4.4 +/- 0.7 kPa (13 +/- 2 to 33 +/- 5 mm Hg) (p < 0.001); cardiac output (CO) fell from 0.28 +/- 0.05 to 0.20 +/- 0.07 liters/kg/min (p < 0.01); mean arterial blood pressure (Psa) decreased from 9.5 +/- 1.2 to 7.9 +/- 1.9 kPa (71 +/- 9 to 59 +/- 14 mm Hg) as did pH from 7.49 +/- 0.04 to 7.13 +/- 0.17 (p < 0.001). Dynamic lung compliance (Cdyn) also decreased; however, pulmonary resistance (RI) remained unchanged. Thromboxane B2 (TxB2) rose in all animals at 60 min coincident with Psa elevation and was significantly blocked by Indo (p < 0.03). In the Indo+TNF group the early TNF-induced rise in Psa was blunted compared to the TNF group [2.9 +/- 1.2 vs. 3.6 +/- 0.8 kPa (22 +/- 3 vs. 27 +/- 6 mm Hg; p < 0.04)] as were the late decreases in pH and Psa (p < 0.04). There were no significant changes in Cdyn secondary to Indo. Although delayed, the hemodynamic changes observed with TNF infusion are similar to those reported for piglets receiving group B streptococci; however, in contrast to the latter the early changes secondary to TNF are only mildly effected by indomethacin. The significant improvement in the late occurring hypotension and acidosis suggests that TNF may act in part via the cyclooxygenase pathway as a mediator of the late hypotension associated with sepsis.
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PMID:Cardiopulmonary effects of tumor necrosis factor-alpha in the piglet: influence of cyclooxygenase inhibition. 883 89


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