Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various studies have shown that in vitro production of cytokines by leukocytes from the newborn are normal, decreased, or increased. We investigated the blood levels of tumor necrosis factor-alpha (TNF-alpha) interleukin-1 alpha, interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) simultaneously to assess the cytokine response to systemic infection during the neonatal period. One or more cytokine levels were elevated in all of the newborns with sepsis. Serum TNF levels in the newborns with sepsis were significantly higher than the two control groups (P < 0.002). Serum IL-6 levels in the study group were also found to be significantly higher than the control groups (P < 0.0004 for sepsis vs adult controls and P < 0.03 for sepsis vs newborn controls). We could not find statistically significant correlation between any of the cytokine levels, C-reactive protein, white blood cells, and platelet counts and the outcome. Gram-negative bacteria were the main causative agents in these patients, although one of them was infected with gram-positive bacteria, besides one premature infant (29 weeks) with Candida sepsis also had significantly elevated TNF, IL-1 beta, and IL-6 levels. Our data show that both mature and premature neonates were able to produce and significantly increase the blood levels of the cytokines in response to sepsis. Because the biologic relevance of cytokine levels is not known, further prospective and sequential studies on cytokine levels simultaneously and correlation with clinical parameters are needed to clarify the biological role of this important component of the host defense system.
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PMID:Neonatal tumor necrosis factor, interleukin-1 alpha, interleukin-1 beta, and interleukin-6 response to infection. 794 22

The aim of this study was to examine if TNF alpha and IL-6 plasma levels could be of value in diagnosing neonatal sepsis. Tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) plasma levels were determined in 15 newborn infants with confirmed sepsis (group I), 18 with suspected sepsis (group II) and 22 control infants (group III). In 33 newborns, initially suspected of having sepsis (groups I and II), a positive test result for plasma concentration of TNF alpha (> 70 pg/ml) had a sensitivity of 73% and a specificity of 94%. A positive test result for IL-6 (> 500 pg/ml) had a sensitivity of 80% and a specificity of 78%. When plasma levels of TNF alpha and IL-6 were combined for the diagnosis of neonatal sepsis, a positive test result for both tests had a sensitivity of 60% and a specificity of 100%. When both tests are positive the diagnosis of neonatal sepsis is almost certain (likelihood ratio = infinity). The combination of TNF alpha and IL-6 determinations appears to be a good predictor of neonatal sepsis.
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PMID:Diagnostic value of plasma levels of tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) in newborns with sepsis. 794 97

This study examined the kinetics of IL-6 release into the systemic circulation in a porcine model of bacterial sepsis induced by infusion of live Pseudomonas aeruginosa. Three groups of animals were studied. Group I (n = 12) animals received a 1 hr infusion of live P. aeruginosa. Group II (n = 6) animals received monoclonal antibody to tumor necrosis factor-alpha (TNF-alpha) (15 mg/kg) prior to induction of sepsis. Group III (n = 7) animals received sterile saline only. TNF-alpha and interleukin-6 (IL-6) levels rose sharply, in group I following pseudomonas infusion. Following a peak at 120 min after the bacterial infusion (4.8 +/- 0.7 U/ml at 120 min vs 0.4 +/- 0.2 U/ml at 0 min), TNF-alpha levels subsequently declined prior to the end of the experiment. In contrast, IL-6 levels rose sharply, subsequent to TNF-alpha, peaked at 180 min, and remained significantly elevated throughout the study period (5.3 +/- 0.9 ng/ml vs 0.05 +/- 0.01 ng/ml, 0 min). In animals pretreated with monoclonal antibody to TNF-alpha, no increase in TNF-alpha activity was detected at any time during the period of study. IL-6 levels in antibody-treated animals, although greatly attenuated, still rose significantly above baseline (2.02 +/- 0.8 ng/ml at 180 min vs 0.05 +/- 0.01 ng/ml at 0 min) and above levels in control animals. We conclude that although TNF-alpha plays an important role in synthesis and release of IL-6, there is a TNF-alpha-independent pathway for release of IL-6 in sepsis.
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PMID:Monoclonal antibody to tumor necrosis factor-alpha attenuates plasma interleukin-6 levels in porcine gram-negative sepsis. 796 99

Circulating interleukin-6 (IL-6) concentrations correlate with disease activity in severe inflammatory conditions, in sepsis and in some hematological malignancies. On the other hand, IL-6 is a potent stimulator of osteoclastogenesis and has been implicated as a contributory factor in the genesis of osteopenic conditions. We measured circulating IL-6 levels by a sensitive (detection limit of 10 U/ml) and specific bioassay in 103 patients with advanced cancer, including 41 with tumor-induced hypercalcemia before any specific hypocalcemic therapy. We related IL-6 concentrations to clinical features and to biochemical parameters of bone metabolism, including blood Ca, Ca2+, Pi, intact parathyroid hormone, parathyroid hormone-related protein, osteocalcin, 1,25-(OH)2-vitamin D and, as markers of bone resorption, the fasting urinary excretion of calcium (Ca/creatinine) and hydroxyproline. IL-6 levels were increased, i.e. detectable, in 23% of the patients, 8/41 (20%) hypercalcemic and 16/62 (26%) normocalcemic patients (NS); the distribution of the values was similar in the two groups. The presence of increased IL-6 concentrations was not related to any clinical characteristic, notably not to the survival nor to the existence of bone metastases, whether in hypercalcemic or normocalcemic patients; e.g., only 3/12 (25%) hypercalcemic subjects without bone metastases had elevated IL-6 levels. We found no significant correlations between IL-6 concentrations and any of the biochemical parameters studied. Hypercalcemic subjects with increased IL-6 had higher urinary Ca/creatinine levels than patients with normal IL-6 levels (P < 0.005) but this was not the case in normocalcemic subjects. Mean concentrations of inflammatory or other bone metabolism markers were not significantly different between patients with normal or with elevated IL-6 levels. In summary, circulating IL-6 levels were increased in 23% of 103 patients with advanced cancer, but the frequency of increased IL-6 concentrations was not related to the presence of hypercalcemia or to any marker of calcium metabolism or bone turnover. The pathogenic importance of circulating IL-6 in patients with solid tumors remains to be demonstrated and our data indicate that increased circulating levels of IL-6, possibly reflecting the activation of the immune system, only contribute in a minor way to the osteolytic process in patients with tumor-induced hypercalcemia.
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PMID:Circulating concentrations of interleukin-6 in cancer patients and their pathogenic role in tumor-induced hypercalcemia. 798 59

As procalcitonin concentrations have been shown to be elevated in patients with septicemia and gram-negative infections in particular, we proceeded to investigate the effect of endotoxin, a product of gram-negative bacteria, on procalcitonin concentrations in normal human volunteers. Endotoxin from Escherichia coli 0113:H10:k, was injected i.v. at a dose of 4 mg/kg BW into these healthy volunteers. Blood samples were obtained before and 1, 2, 4, 6, 8, and 24 h after injection of the endotoxin. Each patient's cardiovascular and overall clinical status was monitored over this period. The patients developed chills and rigors, myalgia, and fever between 1-3 h. Tumor necrosis factor-alpha levels increased sharply at 1 h and peaked at 90 min, reaching the baseline concentration thereafter by 6 h. Interleukin-6 levels increased more gradually, peaking at 3 h and reaching the baseline concentration at 8 h. The procalcitonin concentration, which was undetectable (< 10 pg/mL) at 0, 1, and 2 h, was detectable at 4 h and peaked at 6 h, maintaining a plateau through 8 and 24 h (4 ng/mL). There was no elevation of calcitonin concentrations, which remained below 10 pg/mL, the lowest sensitivity of the assay. Procalcitonin was measured by a two-antibody immunoradiometric assay specific for this peptide, with no cross-reactivity with calcitonin, katacalcin, or calcitonin gene-related peptide. We conclude that endotoxin induces the release of procalcitonin systemically, that this increase is not associated with an increase in calcitonin, and that the increase in procalcitonin associated with septicemia in patients may be mediated through the effect of endotoxin described here. Whether procalcitonin participates in the mechanisms underlying inflammation remains to be investigated.
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PMID:Procalcitonin increase after endotoxin injection in normal subjects. 798 63

Using a recently developed hepsulfam-induced pancytopenia model in rhesus macaques, we have studied the effects of recombinant human interleukin-6 (rhIL-6) and rhIL-3 on marrow regeneration. Control animals were given hepsulfam (1.5 g/m2 by a single 30-minute intravenous [i.v.] injection, n = 4), while study animals received hepsulfam followed by rhIL-6, rhIL-3, or a combination of rhIL-6 and rhIL-3 (n = 3 per study group). Each cytokine was administered by once-daily subcutaneous (SC) injection (15 micrograms/kg/d) for 3 weeks beginning the day after chemotherapy (days 2 through 22). Mean platelet counts in control animals were < 100,000/microL on days 15 through 24, with 50% of the counts < 50,000/microL and two of four animals requiring platelet transfusion. In the rhIL-6- and rhIL-6/rhIL-3-treated groups, the nadir mean platelet counts were 164,000 +/- 58,700/microL and 162,300 +/- 23,800/microL, respectively, and occurred on day 15. Platelet counts in the rhIL-3-treated group were similar to those in controls. Mean absolute neutrophil counts (ANCs) < 1,000/microL occurred on days 10 through 29 in control animals, days 8 through 15 in rhIL-6-treated animals, and days 6 through 8 and 13 in rhIL-6/rhIL-3-treated animals. The frequency of ANCs < 500/microL was significantly less in the rhIL-6- and rhIL-6/rhIL-3-treated groups versus control groups (2.7 +/- 0.6 and 2.0 +/- 1.0 vs 7.0 +/- 1.4 occurrences, respectively; P < .05). rhIL-3-treated animals had ANCs similar to those in controls; one animal died with septicemia on day 21. Monkeys receiving rhIL-6 were significantly more anemic during the cytokine administration period; however, the anemia resolved by day 24. Coadministration of rhIL-3 and rhIL-6 partially corrected the anemia. The data indicate that rhIL-6 prevents significant thrombocytopenia and shortens the neutropenic period in this chemotherapy model.
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PMID:Effect of recombinant human interleukin-6 (rhIL-6) and rhIL-3 on hematopoietic regeneration as demonstrated in a nonhuman primate chemotherapy model. 801 31

The addition of recombinant human interleukin-6 (rIL-6) to either soleus or extensor digitorum longus (EDL) muscle preparations did not affect the rate of protein breakdown as measured by the rate of tyrosine released to the medium. In addition, the presence of the cytokine did not influence either the rate of protein synthesis or that of alpha-(methyl)-aminoisobutyric acid (MeAIB) uptake by the muscle preparations. It is concluded that IL-6 is not the mediator in activating muscle protein turnover during sepsis in the rat.
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PMID:Interleukin-6 does not activate protein breakdown in rat skeletal muscle. 812 60

Thermal injury induces significant physiologic responses of acute inflammation, acute phase reaction and cell repair and growth, mediated by interleukins, cytokines and growth factors. To determine the relative role of interleukin-2 (IL-2) and interleukin-6 (IL-6) in the acute phase of thermal injury, 60 patients (47 men and 13 women, with average age of 37 years [1.5 to 70.0 years]) were analyzed within the first 36 hours and at five to seven days postoperatively. The patient population was categorized by percent burn (2 or 3, or both, degrees): less than 20 percent, n = 22; 20 to 40 percent, n = 18, and greater than 40 percent, n = 20. The average percent burn was 32 percent (range 4 to 95 percent). The mechanism of injury was by flame (25 instances), explosion and flame (19 instances), scald (12 instances), electric (three instances) or chemical (one instance). Twelve patients had an associated inhalation injury; 14 patients had sepsis syndrome. The overall mortality rate was 13 percent. Within 36 hours of onset of injury, IL-6 and IL-2 levels increased in proportion to the severity of the burn wound size. IL-2 levels were significantly elevated in the 20 to 40 percent burn group as compared with the greater than 40 percent group and patients in a control group (p < 0.0001). IL-6 levels increased with burn wound size and were significant only in the greater than 40 percent group (p < 0.0007). Any physiologic modulation of the thermal injury by biologic modifiers must be adapted to the extent of burn wound size and phase of injury: acute, recovery or reparative for optimal benefit and results.
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PMID:Interleukin-2 and interleukin-6 in relation to burn wound size in the acute phase of thermal injury. 814 35

Interleukin-6 is a pleiotropic cytokine and may be a pivotal mediator in the pathogenesis of shock and sepsis, in modulating megakaryocytopoiesis, and in inhibition of tumor growth. Among characteristics of interleukin-6 are regulation of expression of other cytokines, induction of differentiation and proliferation of normal and malignant cells, and inhibition of tumor growth in vivo under experimental conditions. As a major inducer of the acute phase response, interleukin-6 is produced and sets off a chain of events as it acts on effector targets. Preclinical anti-tumor studies with interleukin-6 have provided rationale for probing its role in the therapy of malignancy. The probability is that in the near future interleukin-6 will have established clinical roles as a protein of diagnostic and therapeutic import.
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PMID:Interleukin-6: a cytokine with potential diagnostic and therapeutic roles. 820 Dec 59

Plasma interleukin-6 (IL-6) was higher in patients with disseminated intravascular coagulation (DIC) than in those without DIC. Levels of IL-1 beta and TNF alpha were also significantly higher in patients with DIC. Plasma IL-6 was highest in patients with underlying sepsis and was also high in those with advanced solid cancer. Levels were high in some patients with acute promyelocytic leukaemia and were significantly higher in patients with organ failure than in those without this complication. Plasma IL-6 was higher in DIC patients showing a poor response to therapy than in those with a good response. Incubation with IL-6 caused significant increases in tissue factor activity in mononuclear cells and release of plasminogen activator-1 antigen from human umbilical vein endothelial cells. As increases in IL-6 might give rise to hypercoagulable and hypofibrinolytic states, this may be a cause of DIC and be related to prognosis and organ failure.
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PMID:Increased plasma level of interleukin-6 in disseminated intravascular coagulation. 821 55


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