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Query: UMLS:C0243026 (sepsis)
 52,417 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

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

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

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

Fatal infections in severely burned patients are often preceded by a decline in the production of colony-stimulating factor (CSF) and the proliferation of granulocyte-macrophage stem cells (CFU-GM), and overwhelming sepsis is often associated with leukopenia. The underlying mechanisms accounting for these granulopoietic defects are poorly understood, but the fact that postburn serum has been shown to inhibit CSF production suggests that a humoral factor or factors may play a role. Previous work has demonstrated that plasma levels of lactoferrin (LF), a known inhibitor of CSF production, are elevated following burn injury. To determine if LF is responsible for serum-mediated inhibition of CSF production, serial plasma levels of LF were measured in 18 burn patients using an enzyme-linked immunoabsorbent assay (ELISA). LF was elevated within 24 hours of injury and was associated with an absolute granulocytosis which rapidly declined, reaching a nadir at postburn days 3 through 5. Postburn serum, especially when collected during the first 24 hours following burn injury, inhibited in vitro CSF production by normal human peripheral blood mononuclear cells. Pre-incubation of postburn serum with an LF antibody restored normal CSF production. These data suggest that LF may play an important role in the regulation of postburn granulopoiesis.
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PMID:Inhibition of colony-stimulating factor (CSF) production by postburn serum: negative feedback inhibition mediated by lactoferrin. 326 9

Cerebrospinal fluid measurements of lactoferrin and alpha-1-antitrypsin showed significant elevation in bacterial meningitis in children. 8 of 10 lactoferrin values and 6 of 11 alpha-1-antitrypsin values were above the upper range of controls. Both proteins correlated well with the total number of leukocytes in the cerebrospinal fluid. C-reactive protein, measured by either agglutination or radial immunodiffusion in the cerebrospinal fluid, failed to demonstrate any usefulness in diagnosing bacterial meningitis. Neither elevated serum C-reactive protein in cases of bacterial meningitis, nor sepsis, gave detectable concentrations of C-reactive protein in the cerebrospinal fluid.
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PMID:Lactoferrin, C-reactive protein, alpha-1-antitrypsin and immunoglobulin GA in cerebrospinal fluid in meningitis. 348 45

Degradation of structural elements and excessive consumption of humoral factors, especially of plasma proteinase inhibitors, by proteolysis and/or oxidation is a major cause of multiple organ failure in sepsis or septic shock. Such pathobiochemical reactions seem to be induced primarily by extracellularly liberated lysosomal proteins from PMN granulocytes (e.g. elastase, cathepsin G, myeloperoxidase, lactoferrin) as well as oxygen radicals produced during extensive phagocytosis. In clinical studies on septicemia and septic shock the consumption of plasma proteins including proteinase inhibitors was inversely correlated to the liberation of lysosomal factors, especially the granulocytic elastase. Administration of relatively specific elastase-cathepsin G-inhibitors (Bowman-Birk inhibitor, eglin) in experimental septicemia proved to be a promising therapeutic approach to reduce consumption of plasma proteinase inhibitors and development of interstitial lung edema in severe inflammation.
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PMID:Pathobiochemistry of sepsis: role of proteinases, proteinase inhibitors and oxidizing agents. 352 75

The interrelationships between various components of the non-immune inflammatory response (white cell count, plasma lactoferrin, C-reactive protein, ferritin, iron and iron-binding capacity), were studied serially in a variety of inflammatory conditions including acute lobar pneumonia, active pulmonary tuberculosis, rheumatoid arthritis on gold therapy and sepsis in the face of marrow hypoplasia induced by chemotherapy. Lactoferrin concentrations paralleled the white count in all groups. They were highest in pneumonia and tuberculosis, mildly elevated in rheumatoid arthritis and markedly decreased in neutropenic sepsis. Very high initial lactoferrin concentrations were associated with a poor prognosis in acute pneumonia. C-reactive protein and ferritin concentrations remained elevated through the period of study in acute pneumonia and neutropenic sepsis, while they gradually normalised over weeks in subjects with tuberculosis or rheumatoid arthritis on therapy. In pneumonia and tuberculosis moderate hypoferraemia and a reduced iron-binding capacity were evident. In contrast, a raised percentage saturation was present in neutropenic sepsis, probably related to erythroid marrow suppression. Comparisons between ferritin, lactoferrin and C-reactive protein in the various groups supported the concept that ferritin behaves in part as an acute phase reactant and that hypoferraemia in inflammation is due to deviation of iron into ferritin stores. The suggestion that lactoferrin is responsible for the hypoferraemia and hyperferritinaemia was not supported by the present data. Iron deficiency appeared to limit the hyperferritinaemic response in rheumatoid arthritis, while erythropoietic inhibition by chemotherapy dampened the hypoferraemic response in neutropenic sepsis.
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PMID:The non-immune inflammatory response: serial changes in plasma iron, iron-binding capacity, lactoferrin, ferritin and C-reactive protein. 378 68

Twenty burned patients were studied (with mean body surface area burned 46.5%, mean age 25.4 years, and mean survival probability 78%), and lactoferrin, white-cells count and blood cultures were determined. Lactoferrin was detected more frequently (P less than 0.01) in the samples of patients with positive blood cultures. The role of lactoferrin in host defense mechanism and its possible function in sepsis is considered.
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PMID:Lactoferrin serum levels in burned patients. 315 85

Burns wound sepsis is not only the most common but also the most severe complication following extensive thermal injury. One conceivable explanation of this problem is a reduced capacity of the polymorphonuclear neutrophil leucocytes of these patients to combat the invading microbes. Fifty patients (42 male and 8 female) with deep dermal burns, covering 20-90 per cent of the total body surface area, were investigated from immediately after the injury until death or until healing of the wounds. The following functions of the neutrophil granulocytes were studied: chemotaxis and random migration utilizing a modified Boyden chamber technique, phagocytosis of Staph. aureus and IgG-coated latex particles, bactericidal capacity, e.g. killing of Staph. aureus and the neutrophil granulocyte content of: myeloperoxidase, lactoferrin, and chymotrypsin-like cationic protein. The presence of stimulators and inhibitors of the granulocyte functions was studied using gel filtration of the patient's serum on Sephacryl gel columns. Sera from all patients obtained within the first 1-3 days post-burn contained significantly increased amounts of heat-labile chemokinetic stimulating activity. Sera obtained between days 4 and 10 after injury contained significantly decreased amounts of heat-stable chemokinetic stimulating activity. Reduced chemokinetic activity was found during the third and fourth weeks following major burns (greater than or equal to 40 per cent) due to the presence of one or both heat-stable chemokinetic inhibitory activities. During the second week post-burn patients with burns larger than 40 per cent of the body surface area who showed an inhibition of chemotaxis, also had defects in phagocytosis, and often impaired bactericidal capacity concomitant with lower contents than normal of the granular enzymes. A hyaluronic acid preparation in low concentrations was found to counteract the migration inhibitory effect demonstrated in vitro in sera from patients with severe burns. Based upon these results a series of patients with severe burns and impaired functions of the neutrophil granulocytes have been treated with small amounts of this hyaluronic acid preparation subcutaneously. Very promising results have been noticed, similar to those found in vitro.
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PMID:Neutrophil granulocyte functions in severely burned patients. 402 46


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