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

Leukocyte activation is a property of systemic infection. Animal experiments indicate interleukin-1 (IL-1) as a possible modulator, while contradictory results have been reported from in-vitro stimulation of isolated leukocytes. The purpose of the present study was to investigate the activation of isolated polymorphonuclear (PMN) leukocytes in vitro by preparations of recombinant human IL-1 beta and IL-1 receptor antagonist, which in earlier studies could elicit and abrogate, respectively, a sepsis-like syndrome in rabbits. They have also been shown to influence acute phase protein synthesis in mice and rats, and release of leukocyte cathepsin G in vivo. It was found that recombinant human IL-1 beta elicited a dose-dependent luminol-enhanced chemiluminescence response in isolated human PMN leukocytes in the dose range 8.8 x 10(-11)-8.8 x 10(-8) M. The effect could be blocked by prior treatment with the IL-1 receptor antagonist, indicating a direct effect on the specific IL-1 receptor. Preincubation by IL-1 beta enhanced the effect of a secondary challenge with phorbol 12-myristate 13-acetate or formyl-Met-Leu-Phe by 30-40%. The priming effect of rhIL-1 beta could also be blocked by the specific receptor antagonist. In this study, incubation of PMN leukocytes with rhIL-1 beta failed to induce degranulation of both azurophil (neutrophil proteinase 4/proteinase 3) and specific (lactoferrin) granules. rhIL-1 beta has been shown to induce degranulation in vivo, which is thus indicated as an indirect effect. We conclude that IL-1 beta is a direct and specific, but probably weak stimulator of the PMN leukocyte.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulation of human polymorphonuclear leukocytes by recombinant human interleukin-1 beta. 162 64

Tumor necrosis factor (TNF) has been implicated as a proximal mediator of the septic syndrome. To evaluate the possible role of TNF in leukocyte activation in septicemia, we performed a cross-over saline-controlled study in six healthy men who were intravenously injected with recombinant human TNF (50 micrograms/m2), and analyzed changes in circulating white blood cells and parameters for neutrophil and monocyte activation. TNF elicited a very rapid neutropenia, reaching a nadir after 15 minutes, followed by a neutrophilia. Lymphocytes showed a sustained decrease, whereas monocytes declined transiently. TNF injection was also associated with neutrophil activation, as reflected by a mean fivefold increase in the plasma concentrations of elastase-alpha 1-antitrypsin complexes and a mean sevenfold increase in plasma lactoferrin levels. Serum neopterin, a marker of monocyte activation, was significantly increased 24 hours after the administration of TNF. These changes occurred in the absence of detectable complement activation, as indicated by unchanged C3a-desarg plasma values. Serum interleukin-6 showed a nearly 40-fold increase after TNF injection, whereas interleukin-1 remained undetectable throughout. We conclude that the systemic release of TNF, triggered early after invasive infection, may be involved in the alterations in circulating leukocyte numbers and in the activation of leukocytes, during the development of the septic syndrome.
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PMID:Effects on leukocytes after injection of tumor necrosis factor into healthy humans. 173 11

Increased vasopermeability and vasodilation, presumably the result of endothelial perturbation, are considered among the basic pathogenetic mechanisms in septic shock. Neutrophils have been implicated as a source for mediators in endothelial injury. We measured elastase-alpha 1-antitrypsin (alpha 1AT) complexes and lactoferrin as markers for release of neutrophil granule contents in plasma from patients with sepsis on admission to the Intensive Care Unit, and we delineated the relationship of neutrophil activation to other inflammatory parameters and to hemodynamic and biochemical parameters. Levels of elastase-alpha 1AT and lactoferrin significantly correlated with each other (r = 0.58; p less than 0.008), and were increased (greater than 3.33 and 5 nmol/L, respectively) in 96% and 71% of the patients, respectively. Lactoferrin, but not elastase-alpha 1AT, correlated with the number of white blood cells (r = 0.38; p = 0.008). Elastase-alpha 1 AT levels were significantly higher (p = 0.008), whereas white blood cell counts were lower (p = 0.015) in patients with shock when compared with patients without abnormal blood pressure. Both elastase-alpha 1AT and lactoferrin levels correlated with lactate levels (r = 0.33; p = 0.024 and r = 0.30; p = 0.04), suggesting a role for neutrophil activation in the pathogenesis of hypoxygenation. In addition, elastase-alpha 1AT correlated with the concentrations of interleukin 6 (IL-6) (r = 0.46; p = 0.001) and C3a (r = 0.38; p = 0.009), suggesting that cytokines and complement may contribute to the degranulation of neutrophils in sepsis. Elastase-alpha 1AT complexes were inversely related to C1-inhibitor (r = -0.33; p = 0.028) and to platelet numbers (r = -0.42; p = 0.003). Levels of elastase-alpha 1AT complexes in plasma appeared to be of prognostic significance; levels were higher in 27 patients who died than in 21 patients who survived (p = 0.01). The mortality in 27 patients with concentrations below 10 nM was 37%, whereas it was 81% in 21 patients with higher levels. The overall mortality in this study was 56%. These results provide further evidence that activation and degranulation of neutrophils, induced by multiple agonists, are involved in the development of fatal complications in patients with sepsis.
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PMID:Plasma elastase alpha 1-antitrypsin and lactoferrin in sepsis: evidence for neutrophils as mediators in fatal sepsis. 174 Jun 29

Typical alterations of the white blood cell count are often missed during the acute course of infectious diseases. Activiation and degranulation of granulocytes are followed by elevation of E alpha 1 PI and lactoferrin plasma concentrations under these conditions. The aim of our study was the evaluation of the diagnostic significance of these granulocyte parameters in relation with the absolute granulocyte count in infected pediatric patients. A total number of 106 patients at the age of 1 day to 16 years were studied. 25 children suffered from viral, 26 from localized and 23 from systemic bacterial infections, 32 children exhibiting no signs of infection served as controls. Results of the study are given as medians and ranges. Total granulocyte count was elevated above controls (4.8; 2.2-12.7/nl) only in patients with localized bacterial infections (13.3; 5.5-36.5/nl). E alpha 1 PI and lactoferrin plasma concentrations correlated well (r = 0.72) and were found to be significantly elevated in patients with localized bacterial infections (856; 363-4820 micrograms/l and 748; 206-2078 micrograms/l) and septicemia respectively (661; 256-2078 micrograms/l and 871; 160-9550 micrograms/l). A clearcut differentiation of septic and locally infected patients was given by the ratio of E alpha 1 PI and total granulocyte counts. Significantly elevated E alpha 1 PI concentrations of patients exhibiting viral infections (295; 86-690 micrograms/l) may suggest effective granulocyte activation under this condition. Finally we conclude that E alpha 1 PI and lactoferin plasma concentration related to total granulocyte counts in infected patients may serve as a helpful indicator of granulocyte activation during the acute course of the disease.
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PMID:[Elastase-alpha 1-proteinase inhibitor complex (E alpha 1 PI) and lactoferrin plasma concentrations in viral and bacterial infections]. 203 54

Neutrophils are activated during sepsis. To find out whether granulocytes are further activated during hemodialysis with cellulosic and noncellulosic membranes, we compared the plasma levels of the main granulocyte components in patients with chronic uremia who were undergoing regular hemodialysis treatment and patients with acute renal failure with and without sepsis. During hemodialysis with cuprophane dialyzers, plasma-granulocyte elastase, in complex with alpha-proteinase inhibitor, and lactoferrin levels increased in patients who were undergoing regular hemodialysis treatment, but these levels increased further in patients with acute renal failure who did not have sepsis. Maximal neutrophil degranulation was observed in patients with acute renal failure and sepsis. There was only mild degranulation in all three groups during dialysis with dialyzers made of polysulfone. Our data demonstrate that neutrophil activation is increased in patients with acute renal failure, and it is increased further by superimposed sepsis. Cellulose-containing dialysis membranes introduce a further activation of neutrophils.
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PMID:Neutrophil activation in acute renal failure and sepsis. 233 Dec 24

Total serum iron, plasma lactoferrin and circulating leukocytes were measured in piglets during the early phase of severe gram-negative septicemia and endotoxemia in 3 experimental settings: intravenous (i.v.) infusion of lipopolysaccharide (LPS) (n = 8), i.v. infusion of live Escherichia coli (n = 7) and intraperitoneal (i.p.) infusion of E. coli (n = 6). Iron dropped significantly during the first 30 min of LPS infusion from a median of 32 microM to 13.4 microM. A similar decrease in serum iron was demonstrated in the 2 other groups with minimum values at 120 min after the start of E. coli infusion. Plasma levels of lactoferrin increased significantly 120 min after the start of LPS infusion (median 6 mg/l) when compared to preinfusion values (0.25 mg/l). After i.v. infusion of E. coli a significant rise of plasma lactoferrin was demonstrated already 30 min after bacterial infusion (to 2.1 mg/l) compared to preseptic values (0.8 mg/l). This increase was accompanied with a significant drop of circulating leukocytes (to 7.3 x 10(9)/l) compared to before the infusion (17 x 10(9)/l) in the pigs given E. coli i.v. After i.p. E. coli infusion no significant change of plasma lactoferrin was observed. The rapid fall of total serum iron seen during endotoxemia and E. coli septicemia may in part be explained by the release of lactoferrin from granulocytes and the clearance of iron-bound lactoferrin in the blood or peritoneal cavity.
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PMID:Early fall of circulating iron and rapid rise of lactoferrin in septicemia and endotoxemia: an early defence mechanism. 269 51

A lethal case of Adult Respiratory Distress Syndrome (ARDS) consequent to meningococcal septicemia is clinically and physiologically described. Very high levels of eosinophil cationic protein and lactoferrin in bronchoalveolar lavage were observed in spite of peripheral eosinopenia and neutropenia. These findings provide support for the hypothesis that activated granulocytes are involved in the pathogenesis of septic-induced ARDS.
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PMID:Lethal adult respiratory distress syndrome after meningococcal septicemia biochemical markers in bronchoalveolar lavage. 301 31

The levels of plasma lactoferrin (LF) in response to endotoxin and Escherichia coli infusions in piglets were studied to obtain exact time relation of plasma LF increase in relation to start of endotoxin and E. coli infusions. A new enzyme-linked immunoassay of swine LF is presented. 13 piglets had a 10-fold rapid increase of plasma LF concentrations after 0.25 mg/kg endotoxin intravenous infusion. The initial rise was 3.4 mg/l/h. 14 piglets, receiving 1 x 10(11) E. coli intravenously, showed a higher increase of plasma LF concentrations, amounting to 6-9 mg/l/h. Thus, plasma LF was an early marker of septicemia and endotoxemia.
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PMID:Lactoferrin as an indicator of septicemia and endotoxemia in pigs. 306 32

Immunoluminometric assays for lactoferrin and elastase-alpha 1-proteinase inhibitor complexes were developed using solid-phase methodology, which has already been published from this laboratory. The aim of the study was to develop a rapid method to see whether elevated granulocyte activity was present in the lung, as for example in neonatal sepsis. The lactoferrin assay gave reliable results within 30 minutes, the elastase-alpha 1-proteinase inhibitor complexes, within 5 hours. The correlation between both analytes was good, so that the lactoferrin assay could replace the elastase-alpha 1-proteinase inhibitor assay in emergency cases. The lactoferrin assay was used for rapid answer, the elastase-alpha 1-proteinase inhibitor complex assay for "fine" monitoring of the progress of the disease. Both assays could be used to measure concentrations in plasma or bronchoalveolar lavage using a 10 microliters sample. Plasma for the elastase-alpha 1-proteinase inhibitor complex determination had to be diluted 1:50 before being assayed. Only EDTA plasma was used in the assay, as either heparin plasma or serum resulted in granulocyte destruction, thus giving rise to elevated, and non-reproducible results. The results from bronchoalveolar lavage show an excellent correlation between elastase-alpha 1-proteinase inhibitor complexes and lactoferrin. No interference was seen from lipaemic or icteric plasma samples. Results from haemolytic samples i.e. where lysis of erythrocytes and leukocytes had occurred, had to be treated with care if no clinical indication of intravascular haemorrhage was present. The assays lend themselves to perinatal diagnosis, as the total volume of plasma or lavage needed is theoretically under 50 microliters, i.e. ethically acceptable for regular monitoring of neonates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Development and clinical evaluation of immunoluminometric assays for lactoferrin and elastase-alpha 1-proteinase inhibitor complexes in body fluids with special references to bronchoalveolar lavage and neonatal sepsis. 306 29

In healthy subjects normal plasmalactoferrin (PLf) concentrations were found to be 0.206 +/- 0.06 mg/l in 49 men and 0.148 +/- 0.06 mg/l in 62 women. A highly significant correlation of PLf with the number of circulating neutrophils (PMN) and a PLf/PMN relationship suggesting proportionality was demonstrated. Among 73 patients absolute PLf concentrations were significantly increased in septicemia, cirrhosis of the liver and tumors with liver metastases, decreased in localized infection, tumors without liver involvement, iron deficiency and acute hepatitis B, and normal in acute myocardial infarction. The PLf/PMN ratio, on the other hand, was normal in liver cirrhosis, hepatitis B and in a part of the patients with septicemia and tumor disease with liver involvement. The ratio was increased in a part of the septicemic patients, and decreased in the remaining disease types. Positive PLf/PMN correlations were found in myocardial infarction, septicemia and liver cirrhosis, whereas a very close, negative correlation existed in acute hepatitis B. These findings are discussed on the basis of existing knowledge on lactoferrin physiology, the intravascular fate of PMN and the RES function.
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PMID:Plasmalactoferrin and the plasmalactoferrin/neutrophil ratio. A reassessment of normal values and of the clinical relevance. 313 91


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