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)

Fusion proteins of the human 55-kDa TNF receptor extracellular domain with hinge and C2/C3 constant domains of human IgG1 or IgG3 heavy chains were tested in a primate sepsis model. Twenty-four baboons received 4.6, or 0.2 mg/kg of TNFR5-G1,3, or placebo, before the administration of a lethal dose of live Escherichia coli. Treatment with TNFR5-G1,3 decreased 5-day mortality from 88% in the placebo group to 12% in the TNFR5-G1,3-treated animals (p < 0.01 by Fisher's exact test). Treatments with TNR5-G1 and TNFR5-G3 in doses from 0.2 to 4.6 mg/kg were efficacious. Free plasma TNF was neutralized by all treatments, but inactive TNF/TNFR5-G1,3 complexes remained in circulation for prolonged periods. TNFR5-1,3 treatments attenuated the hemodynamic disturbances, reduced fluid requirements, and decreased the systemic IL-1 beta, IL-6, and IL-8 responses. In addition, TNFR5-G1,3 treatment shortened the granulocytopenia and reduced the loss of cellular TNF receptors from granulocytes. The decrease in fibrinogen concentrations and increase in prothrombin and partial thromboplastin times were significantly attenuated by TNFR5-G1,3 treatment. TNFR5-G1,3 treatment markedly attenuated the rise in plasma lactate concentration. Histologic studies of TNFR5-G1,3 revealed dose-dependent protection against tissue injury by Escherichia coli administration.
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PMID:Protection against lethal Escherichia coli bacteremia in baboons (Papio anubis) by pretreatment with a 55-kDa TNF receptor (CD120a)-Ig fusion protein, Ro 45-2081. 869 Sep 12

Sepsis is a constellation of clinical signs and symptoms resulting from excessive systemic host inflammatory response to infection. This inflammatory response is largely mediated by cytokines, which are released into the systemic circulation. Plasma concentrations of specific cytokines, TNF alpha, IL-1 beta, IL-6 and IL-8 are frequently elevated in human sepsis and cytokine concentrations correlate with severity and outcome of sepsis. In addition to pro-inflammatory cytokines, soluble cytokine receptors, cytokine receptor antagonists and counter-inflammatory cytokines are also produced in large quantities in patients with sepsis; however, the specific role of these molecules in sepsis remains undefined. A complex interaction of cytokines and cytokine-neutralizing molecules probably determines the clinical presentation and course of sepsis. Intervening in this sequence of events to modify the host inflammatory responses may prove to be a beneficial treatment strategy for sepsis, but currently tested anticytokine therapies have been largely unsuccessful.
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PMID:Sepsis and cytokines: current status. 870 20

Plasma levels of type II phospholipase A2 (type II PLA2), cytokines and endotoxin were determined in patients with sepsis to investigate their interrelations and their role in the patient's prognosis. Type II PLA2 was measured by radioimmunoassay, tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and IL-8 were each measured by enzyme-linked immunosorbent assay (ELISA). Endotoxin was determined by a method based on an endotoxin-specific synthetic substrate. Plasma levels of type II PLA2 were significantly higher in the patients who died of sepsis than in those who survived the illness. There was a significant correlation between type II PLA2 and TNF-alpha and IL-6. Type II PLA2, TNF-alpha, IL-6, and IL-8 may be useful as indices of disease severity. The results suggest that TNF-alpha and IL-6 stimulate the production of type II PLA2 in the plasma of patients with sepsis.
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PMID:Plasma levels of type II phospholipase A2 and cytokines in patients with sepsis. 874 87

Systemic Inflammatory Response Syndrome (SIRS) is a new concept of entry criteria for sepsis. This concept, when applied to area of Multiple Organ Failure (MOF), is considered to be a preparatory state for MOF. To study the significance of SIRS state at cardiac surgery, we measured the body temperature, white blood cell count, respiratory rate and heart rate of 18 patients who underwent elective cardiac surgery, from the 1st post-operative day to the 7th post-operative day. We also measured Interleukin-6 and 8 (IL-6 and IL-8) to understand the relationship between the SIRS state and inflammatory cytokines just after cardiopulmonary bypass (CPB), at the 1st, 3rd and 6th postoperative day. The result was as follows: Patients with CPB more than 120 minutes have more frequency and longer duration of SIRS than patients with CPB less than 120 minutes. Serum levels of IL-8 at SIRS state were revealed statistically higher than at non-SIRS case. Duration of SIRS state was related to CPB time and serum levels of IL-6 and IL-8 just after CPB. We concluded that SIRS state is an indication for anti-cytokine therapy to prevent MOF, and it is important to shorten CPB time in order to decrease the duration of SIRS.
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PMID:[Significance of systemic inflammatory response syndrome at cardiopulmonary bypass]. 875 88

Many different cellular processes are altered by microenvironmental changes in the oxygen level, particularly hypoxia. In most cases, these hypoxic effects are mediated via alterations in cellular signal transduction pathways. Low oxygen states are generally viewed as deleterious; however, recent studies show that alterations in oxygen levels are physiologically important, influencing cells in a variety of ways. Low oxygen levels can stimulate cellular processes, such as the production of tumor necrosis factor, interleukin (IL)-1, IL-8, and nuclear factor kappa B. Kupffer cell-mediated alterations in cocultured hepatocyte function are altered by pre-exposure to hypoxic culture conditions, whereas superoxide production, intracellular pH, and adenosine triphosphate levels are decreased by hypoxia. Hypoxia followed by reoxygenation stimulates tyrosine kinase enzymes and increases intracellular calcium in a variety of cells. This review highlights recent findings concerning the manner and mechanisms by which low oxygen levels influence cell functions and cellular signaling systems. Detailed information is still lacking about the location and mechanism of most hypoxic-mediated alterations in cell signaling pathways. However, information about how factors altered by trauma and sepsis, such as Po2, acidosis, and endotoxin, effect cellular signaling pathways is rapidly emerging. Understanding the mechanism by which oxygen availability alters cell function will be important to the development of optimal therapies for post-traumatic shock and organ dysfunction.
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PMID:Hypoxic alterations in cellular signal transduction in shock and sepsis. 877 93

IL-8 is a potent neutrophil attractant and activator. IL-8 has been reported to be involved in the pathogenesis of several diseases, including rheumatoid arthritis, sepsis, psoriasis, and the adult respiratory distress syndrome (ARDS). Our previous studies demonstrated that high concentrations of IL-8 were present in alveolar fluids from patients with ARDS and were associated with increased mortality. In this study we report that a major portion of IL-8 in bronchoalveolar fluids from patients with ARDS is associated with anti-IL-8 autoantibody (anti-IL-8:IL-8 complexes). Free autoantibodies that recognize IL-8 were also detected in these fluids. Next, we examined the properties of anti-IL-8 autoantibodies present in lung fluids from ARDS patients and compared them with autoantibodies from normal plasma and arthritic synovial fluids. The anti-IL-8 autoantibody was polyclonal, and IgG3 and IgG4 were the primary IgG subclasses. Anti-IL-8:IL-8 complexes consisted of one IgG and one IL-8 molecule. In addition, anti-IL-8 autoantibody bound IL-8 with a high affinity (approximately 10(-12) M) and inhibited IL-8 interaction with its specific receptors on neutrophils. The results suggest that anti-IL-8 autoantibodies may regulate IL-8 activity.
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PMID:Anti-IL-8 autoantibodies in alveolar fluid from patients with the adult respiratory distress syndrome. 880 76

Tumour necrosis factor (TNF) alpha, interleukin (IL) 1 beta, IL-6 and IL-8 are thought to play a central role in the pathophysiology of sepsis but their role in acute pancreatitis is unknown. In the present study, monocytes were isolated from the peripheral blood of 26 patients with moderate or severe acute pancreatitis without biliary sepsis. Secretion of these cytokines in vitro was measured at intervals during the first week of illness. Sixteen patients developed systemic complications. Peak TNF-alpha secretion was significantly higher in patients who developed systemic complications (median (interquartile range (i.q.r.)) 18.5 (5.5-28.5) ng/ml) than in those with an uncomplicated course (3.7 (2.3-6.4) ng/ml, P < 0.01). Similarly, peak IL-6 and peak IL-8 secretion were significantly higher in the complicated group (IL-6: complicated median (i.q.r.) 48.9 (12.1-71.0) ng/ml, uncomplicated 16.3 (14.2-37.9) ng/ml, P < 0.05; IL-8: complicated 748 (643-901) ng/ml, uncomplicated 608 (496-749) ng/ml), P < 0.05). No significant difference in peak IL-1 beta secretion was observed between the two groups. Systemic complications of acute pancreatitis are associated with a significant increase in monocyte secretion of TNF-alpha, IL-6 and IL-8 suggesting that, as in sepsis, these cytokines play a central role in the pathophysiology of the disease.
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PMID:Increased monocyte cytokine production in association with systemic complications in acute pancreatitis. 881 75

We measured the levels of soluble intercellular adhesion molecule-1 (sICAM-1), CD11a, CD11b, CD18, endotoxin, and various inflammatory cytokines to clarify the relationship between adhesive molecules and cytokines in sepsis. We studied 21 patients with sepsis (sepsis group) and 13 patients with trauma not complicated by infection (trauma group). The mean sICAM-1 level was significantly higher in the sepsis group than in the trauma group. No significant difference was observed in the CD11a, CD11b, and CD18 levels between the two groups. The sICAM-1 levels significantly correlated with the levels of endotoxin, tumor necrosis factor alpha (TNF-alpha), and IL-8, but CD11a, CD11b, and CD18 levels did not correlate with endotoxin or cytokine levels. These findings suggest that ICAM-1 production is induced by endotoxins and cytokines produced in excess by inflammatory reactions and that endotoxins and cytokines are involved in qualitative, but not quantitative changes in LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18).
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PMID:Changes in adhesion molecule levels in sepsis. 882 72

To investigate the involvement of nitrite/nitrate oxide (NOx) in septic shock, and to evaluate the relationships between NOx and cytokines in patients with this disorder, we evaluated 11 patients with septic shock and 12 patients with sepsis unassociated with shock. NOx were measured with an automated system based on the Griess reaction. The plasma concentrations of various cytokines were determined by enzyme-linked immunosorbent assay. Endotoxin was determined by a specific assay after the plasma samples were processed by a perchloric acid method. The mean plasma levels of NOx in the group with shock significantly exceeded those in the group without shock. Significant correlations were observed between the plasma levels of NOx and those of endotoxin, tumor necrosis factor-alpha, and interleukin 8 in both groups. NOx appeared to be involved in the development of septic shock in humans. Endotoxin and cytokines appeared to be involved in the production of NOx.
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PMID:Nitrite/nitrate oxide (NOx) and cytokine levels in patients with septic shock. 882 74

Over a period of 14 days a longitudinal analysis was performed on the effects of filgrastim (recombinant human granulocyte colony stimulating factor, rhG-CSF) administered to 20 postoperative/posttraumatic patients at risk of or with sepsis. The following parameters were determined: leukocyte counts, serum cytokine levels and the surface expression of functional antigens and adhesion molecules. Filgrastim (1 mu g/kg.day) was infused continuously on the first 3 days and tapered to 0.5 mu g/kg.day on the following 4 days or until discharge from the surgical intensive care unit. During infusion of filgrastim, G-CSF levels increased in 16 out of the 20 patients within 48 h. In these 16 patients, leukocyte counts increased in 15 out of 16 patients. Expression of CD64 was upregulated within 24 h. The expression of CD32 was upregulated in 8 out of 9 patients with an initial expression < 55%. LAM-1 expression was downregulated in all patients revealing an initial expression of LAM-1 > 40%. Soluble ICAM increased in 9 out of 11 patients. IL-8 decreased in all 6 patients presenting initial values of IL-8 > 90 pg/ml. IL-1RA increased in 10 patients. Filgrastim had no effect on the expression of CD14, CD16 and CD34 and on the levels of TNF-alpha and sTNF-R type I (p55). In conclusion, infusion of filgrastim in postoperative/post traumatic patients at risk of and with sepsis resulted in improved generation and function of neutrophils and appeared to counterregulate hyperactivation of proinflammatory processes.
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PMID:Filgrastim (RHG-CSF) related modulation of the inflammatory response in patients at risk of sepsis or with sepsis. 883 41


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