Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An assay of interleukin 1 (IL-1) production by human monocytes was used to detect minute amounts of bacterial lipopolysaccharide (LPS) in sera or serum components designed for use in experiments or for injection into humans. Elaboration of IL-1 is a more sensitive criterion for the presence of LPS than is the rabbit pyrogenicity assay, and contamination of a given solution with LPS can be semiquantitatively determined by comparison with a standard. Interaction of (exogenously added) LPS with serum interferes with the recognition of LPS by monocytes but in a manner different from that encountered in the limulus test. Recognition of LPS by monocytes was not affected by the presence of naturally occurring antibodies to LPS. With use of IL-1 elaboration as an indicator, the presence of functionally active LPS in the sera of some patients with sepsis could be demonstrated.
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PMID:Lipopolysaccharide-induced elaboration of interleukin 1 by human monocytes: use for detection of lipopolysaccharide in serum and the influence of serum-lipopolysaccharide interactions. 350 Apr 94

Cord blood monocyte synthesis of IL-1 was investigated by using a thymocyte proliferation assay. Monocytes from 27 infants ranging in gestation from 31 to 41 weeks (mean 38.9, SE 0.54) with birthweights from 1.20 to 4.31 kg (mean 3.24, SE 0.13) were isolated from cord blood; 2 x 10(5) cells/ml were plated in 15 mm wells and stimulated with 10 micrograms/ml LPS (E. coli). Control cultures contained medium alone. Supernatants were harvested after 24 hr and tested in a C3H/HeJ mouse thymocyte proliferation assay. The mean response for 27 cord monocyte samples at 24 hr was 14,142 cpm (SE 1,499), not significantly different than that for cells obtained from eight normal adult volunteers (15,137 cpm, SE 3,535). Vaginally delivered infants with perinatal complications such as amnionitis, fetal distress, or early sepsis had significantly increased unstimulated activity (5,139 vs 1,331 cpm) compared to samples from normal infants, whereas stimulated activity was not significantly different (16,219 vs 12,261 cpm). Thus, the IL-1 response to lipopolysaccharide is intact in newborn human monocytes and there is evidence of an increased unstimulated activity following neonatal complications.
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PMID:Interleukin-1 activity from human cord blood monocytes. 350 46

Accelerated muscle proteolysis is a characteristic of systemic reaction following trauma, sepsis, or extensive thermal injury. The factors involved in this accelerated muscle breakdown have not been fully described. However, recently leukocytic pyrogen or interleukin 1 (IL-1) have been implicated in the induction of muscle protein degradation in septicemia or trauma. The epidermal cytokine epidermal cell-derived thymocyte activating factor (ETAF) is biochemically and functionally similar to IL-1. Injury to skin can augment ETAF activity. Using a murine model, we found that thermal injury can significantly enhance ETAF/IL-1 activity in a dose-dependent fashion. In addition, ETAF can cause net muscle protein breakdown in vitro. Thus, increased amounts of ETAF produced by thermally injured skin may contribute to the accelerated muscle breakdown in extensive thermal injury.
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PMID:Stimulation of muscle protein degradation by murine and human epidermal cytokines: relationship to thermal injury. 353 47

Hepatic insufficiency associated with the multiple-system organ-failure (MSOF) syndrome is a frequent sequellae of sepsis and severe trauma. Although its etiology is poorly understood, there is a growing literature suggesting that it may be mediated in part by secretory products of cells of monocyte/macrophage lineage including Kupffer cells. Several investigators have reported in vitro macrophage/Kupffer cell-mediated cytotoxicity toward target cells following appropriate stimulation. In addition, in vivo hepatocyte toxicity has been documented following activation of the reticuloendothelial system. The role of several secretory products including active oxygen intermediates, neutral proteases, and interleukin 1 in this cell-mediated model of hepatocellular modulation is reviewed.
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PMID:Macrophage-mediated modulation of hepatic function in multiple-system failure. 390 73

Protein degradation in skeletal muscle increases with fever and sepsis. Our studies indicate that prostaglandin E2 (PGE2) is an important regulator of muscle proteolysis that seems to signal this increase in fever. When rat skeletal or cardiac muscles were incubated with arachidonate, rates of protein breakdown rose and protein balance became more negative. Aspirin or indomethacin, which prevented synthesis of PGE2, markedly reduced this effect. By itself PGE2 stimulated proteolysis without altering protein synthesis. PGE2 seems to increase proteolysis in the lysosomes, inasmuch as leupeptin and Ep-475 inhibit this response. These inhibitors inactivate lysosomal thiol proteases in the muscles without affecting the Ca2+-activated protease. (In fact, complete inactivation of the latter enzyme with mersalyl did not reduce overall proteolysis in the muscles). When muscles from feverish rats were incubated in vitro, they showed greater protein breakdown and PGE2 synthesis than muscles from normal animals. Addition of indomethacin eliminated this difference. Leukocytic pyrogen (interleukin 1), a protein released by monocytes that signals the onset of fever, also seems to signal increased muscle PGE2 synthesis and muscle proteolysis. This protein enhanced both processes dramatically in the isolated muscles. These findings suggest that cyclooxygenase inhibitors may be useful in the treatment of patients showing excessive protein breakdown.
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PMID:Control of protein degradation in muscle by prostaglandins, Ca2+, and leukocytic pyrogen (interleukin 1). 632 20

Recent advances in the field of molecular biology have revolutionized our understanding of the functioning of living organisms and facilitated the development of robust tools for both diagnosis and treatment of diseases. With particular reference to the field of critical care medicine, development of molecular biology techniques have aided in the following: (1) rapid and highly specific detection of pathogenic infectious agents (eg, Mycobacterium tuberculosis, Pneumocystis carinii, cytomegalovirus, Legionella); (2) development of assays for measurement of circulating cytokines such as tumor necrosis factor (TNF) and interleukin (IL)-1 that has helped our understanding of the pathogenesis of the sepsis syndrome; (3) administration of antibodies or soluble receptors to attempt to prevent untoward effects of cytokines such as TNF or IL-1; and (4) the administration of recombinant deoxyribonucleic acid (DNA) or proteins to patients in an attempt to alter the course of a disease such as antioxidant enzymes (superoxide dismutase). The rapidity of progress in this field has been staggering, which necessitates frequent updating of our knowledge for clinicians to put these molecular tools to their best use. This brief review attempts to explain the basic principles of commonly used techniques in molecular biology including recombinant DNA, polymerase chain reaction, DNA libraries, gene therapy, and protein biochemistry in a manner that is understandable to those without an in-depth knowledge of the field.
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PMID:Current techniques in cell and molecular biology. 749 50

Vascular endothelium activated by endotoxin (lipopolysaccharide [LPS]) and cytokines plays an important role in organ inflammation and blood leukocyte recruitment observed during sepsis. Endothelial cells can be activated by LPS directly, after its interaction with LPS-binding protein and soluble CD14 in plasma. LPS-LPS-binding protein complexes in blood also interact with monocytes and neutrophils bearing glycosyl-phosphatidylinositol (GPI) anchored membrane CD14 (mCD14), promoting the release of cytokines such as tumor necrosis factor and interleukin 1 (IL-1). These molecules, in turn, have the capacity to activate endothelial cells providing an indirect pathway for LPS-dependent endothelial cell activation. In this work, we address the relative importance of the direct and the indirect pathway of in vitro LPS-induced human umbilical vein endothelial cell (HUVEC) activation. Substituting whole blood for plasma resulted in a 1,000-fold enhancement of HUVEC sensitivity to LPS. Both blood- and plasma-dependent enhanced activation of HUVEC were blocked with an anti-CD14 monoclonal antibody. Blood from patients with paroxysmal nocturnal hemoglobinuria, whose cells lack mCD14 and other GPI anchored proteins, was unable to enhance LPS activation of HUVEC above the level observed with plasma alone. IL-10, an inhibitor of monocyte release of cytokines, decreased the blood-dependent enhancement of HUVEC activation by LPS. Blood adapted to small doses of LPS was also less efficient than nonadapted blood in producing this enhancement. Addition of purified mononuclear cells to HUVEC or the transfer of plasma from whole blood incubated with LPS to HUVEC, duplicated the enhancement effect observed when whole blood was incubated with HUVEC. Taken together, these data suggest that the indirect pathway of LPS activation of endothelial cell is mediated by monocytes and mCD14 through the secretion of a soluble mediator(s). The indirect pathway is far more efficient than the direct, plasma-dependent pathway.
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PMID:A critical role for monocytes and CD14 in endotoxin-induced endothelial cell activation. 750 60

Serum samples from 76 patients with neutropenia and 34 control subjects were analyzed for levels of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin 1 alpha, and tumor necrosis factor beta. Clinical correlates and duration of neutropenia were determined insofar as possible. Systemic acute inflammatory disease was present in only two patients. In most cases, the neutropenia was considered idiopathic or medication related. Significantly elevated serum granulocyte colony-stimulating factor levels were found in the patient group, regardless of the apparent cause of the neutropenia. Increased levels of granulocyte-macrophage colony-stimulating factor, interleukin 1, and tumor necrosis factor were seen in only one patient with sepsis.
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PMID:Serum cytokine levels in patients with neutropenia. 752 20

We and others have proposed that cytokine-stimulated nitric oxide (NO) production is responsible for reversible myocardial depression in sepsis, trauma and ischemia. An effect of NO on cardiac sarcolemmal L-type calcium channels has also recently been proposed. The spontaneous beating rate of neonatal cardiac myocytes is regulated by the sarcolemmal L-type calcium channel. Accordingly, we sought to determine if cytokine-stimulated NO production could also regulate beating rates of neonatal cardiac myocytes. Treatment of neonatal rat cardiac myocytes with TNF, IL-1, IL-6, 10(-5)M NMA, or 10(-3)M NMA significantly enhanced spontaneous beating rates compared to untreated myocytes in serum-free media for 48 hours (p < or = .01; n = 12 for each). Only IL-1 treatment resulted in significant nitrite levels vs. control over 48 hours (4.2 +/- 0.7 vs. 0.3 +/- 0.2 nmoles/1.25 x 10(-5) cells, respectively) (n = 12). Nitrite production by IL-1 was inhibited by 10(-3)M NMA but not 10(-5)M NMA (0.3 +/- 0.2 vs. 4.1 +/- 0.6 nmoles; p < .01; n = 12). The addition of 10(-5)M NMA to TNF, IL-1, and IL-6 did not alter the effect of the cytokines on the spontaneous beating rates of the cardiac cells (p < or = .01; n = 12 for each). These results strongly suggest that cytokines and NMA affect cardiac myocyte spontaneous beating rates through mechanisms independent of NO.
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PMID:Chronotropic effects of cytokines and the nitric oxide synthase inhibitor, L-NMMA, on cardiac myocytes. 752 6

This study assessed the hepatic acute phase response and cellular Ca2+ regulation in septic animals and in hepatoma cell lines in vitro. Sepsis was induced in male Sprague-Dawley rats by implanting in their abdominal cavities fecal pellets impregnated with live Escherichia coli and Bacteroides fragilis. 8 h after implantations, rats were treated with diltiazem (1.2 mg/kg) or superoxide dismutase (SOD) (5 x 10(3) units/kg). After 24 h, plasma acute phase proteins (APP) were determined by immunoelectrophoresis, and hepatic APP-mRNAs by Northern blot hybridization. Effects of diltiazem, verapamil, or SOD on hepatic cells were determined in rat Reuber H-35 and human HepG2 hepatoma cells. Sepsis induced a significant increase in plasma APP and their hepatic mRNAs. Diltiazem and SOD reduced the sepsis-induced elevations in plasma lactate, the febrile response and mortality. APP expression in H-35 and HepG2 cells, stimulated by interleukin 1 (IL-1), IL-6, and dexamethasone, was inhibited by diltiazem or verapamil but not SOD. The results suggest that a heightened hepatic APP response in septic animals accompanies systemic/metabolic derangements and a significant animal mortality. Because diltiazem was previously shown to prevent sepsis-related disturbances in hepatic cellular Ca2+ regulation, its mediation of decrease in APP, systemic/metabolic response, and mortality may be effected through modifications in cellular Ca2+ regulation. The data from hepatoma cells show an attenuation of the AAP can result from direct effects of a calcium blocker. However, whether the blocker primarily modifies cellular Ca2+ regulation and secondarily effects APP gene expression, or directly effects gene expression remains unknown.
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PMID:Diltiazem and superoxide dismutase modulate hepatic acute phase response in gram-negative sepsis. 753 32


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