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)

Recent animal and human studies have suggested that leptin secretion is closely linked to the functions of the hypothalamic-pituitary-adrenal (HPA) axis and the immune system, both of which are crucial in influencing the course and outcome of critical illness. Therefore, we measured basal plasma leptin levels and examined the circadian secretion of leptin, in parallel with the hormones of the HPA axis and a key cytokine, interleukin-6, in critically ill patients with acute sepsis. Sixteen critically ill patients from the University of Leipzig Intensive Care Unit were recruited for this study. All of these patients fulfilled the standard diagnostic criteria for sepsis. Plasma leptin levels were measured in all patients and controls at 09:00. In addition, in a subgroup of eight critically ill patients and all of the nine controls plasma leptin, cortisol, ACTH and interleukin-6 concentrations were measured every 4 hours for 24 hours. Mean plasma leptin levels were three-fold higher (18.9 +/- 4.5 ng/ml) in critically ill patients than controls (3.8 +/- 1.0 ng/ml, p < 0.05). Similarly, ACTH levels were lower (7.8 +/- 3.4 pmol/l) in patients than in controls (17.1 +/- 1.5 pmol/l, p < .001), while plasma cortisol levels were increased (947.6 +/- 144 nmol/l) in patients compared to controls (361.1 +/- 29, p < 0.001). Morning plasma interleukin-6 levels were markedly elevated in all patients with sepsis (1238.0 +/- 543.1 pg/ml) versus controls (6.4 +/- 1.7, p < 0.001). The controls exhibited a nyctohemeral fluctuation in plasma leptin levels with peak levels at 23:00; in contrast, septic patients, had no nocturnal rise of leptin. In healthy controls, plasma leptin and cortisol had reciprocal circadian rhythms with high nocturnal leptin levels and low nocturnal cortisol concentrations; in critically ill patients, this relation was abolished. Mean leptin levels were three-fold higher in patients who survived the septic episode (25.5 +/- 6.2, n = 10) than in non-survivors (8.0 +/- 3.7, n = 6, p < 0.01). We conclude that in addition to its function as an anti-obesity factor, leptin may play a role in a severe stress state such as acute sepsis.
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PMID:Plasma leptin levels are increased in survivors of acute sepsis: associated loss of diurnal rhythm, in cortisol and leptin secretion. 943 56

Both leptin and interleukin-6 (IL-6) are hypersecreted in acute critical illness, such as sepsis. Leptin is produced by adipocytes, it inhibits appetite and stimulates the sympathetic nervous system, thereby reducing adipose mass. IL-6 is produced by immune cells and adipocytes, it reduces the production of other inflammatory cytokines and stimulates release of acute phase proteins by the liver, participating in the control of inflammation. Leptin inhibits, whereas IL-6 stimulates, the hypothalamic-pituitary-adrenal axis. While high IL-6 levels are associated with poor outcome in critically ill patients, the role of leptin in critical illness and its importance for survival are not known. To examine the relation between IL-6, leptin and cortisol in critical illness, we performed frequent 4 h plasma sampling in eight patients on day 1 of intensive care unit admission for acute sepsis. Sampling was repeated on days 3 and 5 in the five survivors. The levels of all three hormones were markedly elevated; there was a lack of the normal diurnal rhythmicity of leptin and IL-6 and a blunted diurnal rhythmicity of cortisol secretion. A strong negative correlation between mean 24 h plasma IL-6 and leptin was revealed. Although such a relationship could possibly be explained by the negative and positive effects of cortisol hypersecretion on each hormone respectively, a negative correlation between leptin and cortisol was detected, whereas there was no significant correlation between IL-6 and cortisol. Mean IL-6 values were higher (1389.5+/-644.9 vs. 658.8+/-250.5) and leptin levels were lower (2.73+/-1.1 vs. 26.5+/-11.6) in the non-survivors than in the survivors. These findings suggest that IL-6 is not the principal stimulus of leptin hypersecretion in critically ill patients with sepsis. The negative relation between IL-6 and leptin is of potential importance, as high IL-6 levels have been associated with poor outcome in critically ill patients, and relatively low leptin levels may impair sympathetic system and immune functions.
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PMID:Leptin and interleukin-6 in sepsis. 993 Jun 30

Circulating leptin concentrations are raised in animal models of inflammation and sepsis. The purpose of this study was to determine the effect of sepsis on serum leptin concentration in humans and to examine the relationship between leptin and the metabolic consequences of sepsis. Resting energy expenditure, insulin sensitivity, and fasting serum leptin, plasma insulin, and cortisol concentrations were measured in 20 subjects with intra-abdominal sepsis and 20 healthy control subjects, before and during a 2-h period of euglycemic hyperinsulinemia. Fasting serum leptin concentrations were similar in septic and control subjects. In simple regression analysis, serum leptin concentrations correlated significantly with percent body fat in both septic patients (r = 0. 64, P < 0.005) and healthy subjects (r = 0.75, P < 0.0001). Multiple regression analyses additionally indicated that percent body fat, fasting plasma insulin, and plasma cortisol, but not sepsis, were significant and independent determinants of serum leptin concentration. No relationship between leptin and resting energy expenditure or insulin sensitivity was identifiable. A major metabolic role for leptin in human sepsis therefore appears unlikely.
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PMID:Serum leptin concentrations and their relation to metabolic abnormalities in human sepsis. 1019 1

Leptin, the ob gene product, has been proposed as a mediator of inflammatory cytokine-dependent decreased food intake and cachexia in rodents. In humans, leptin serum levels increase after administration of tumor necrosis factor-alpha (TNF-alpha) or interleukin-2 or during septicemia. However, the effect of human chronic inflammatory disease on serum leptin is unknown. We therefore determined the serum leptin level (radioimmunoassay), body mass index (BMI), percent body fat ([%BF] bioelectrical impedance analysis), and disease activity (Disease Activity Score [DAS]) in 58 patients with rheumatoid arthritis (RA) and 16 controls. The BMI, %BF, serum leptin, and ratio of leptin to %BF (leptin/%BF) did not differ significantly in 25 patients with moderate RA activity (DAS, 3.6 +/- 0.5), 33 patients with low RA activity (DAS, 1.8 +/- 0.5), and controls. A positive correlation for serum leptin and %BF was detected in all groups. Our data indicate that in RA, a human chronic cytokine-mediated inflammatory disease, the serum leptin level is directly related to %BF but not to disease activity.
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PMID:Leptin serum levels are not correlated with disease activity in patients with rheumatoid arthritis. 1038 Nov 49

Leptin production is increased in rodents by administration of endotoxin or cytokines. To investigate whether circulating leptin is related to cytokine release and survival in human sepsis, plasma concentrations of leptin, interleukin (IL)-6, IL-1beta, tumor necrosis factor (TNF)-alpha, soluble TNF receptor type I, IL-1 receptor antagonist (IL-1ra), and the inflammatory modulator IL-10 were measured as soon as severe sepsis (n=28) or septic shock (n=14) developed and every 6 h for 24 h. Patients with sepsis or septic shock had leptin concentrations 2.3- and 4.2-fold greater, respectively, than the control group. There was an independent association for leptin with IL-1ra and IL-10 in both patient groups. By discriminant analysis, leptin and IL-6 were independent predictors of death. These findings suggest that increases in leptin levels may be a host defense mechanism during sepsis.
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PMID:Relationship of plasma leptin to plasma cytokines and human survivalin sepsis and septic shock. 1043 92

Intensive care patients with organ failure often suffer an acute catabolic state. Leptin is a 16-kDa hormone which is produced by mature adipocytes and correlates with human energy expenditure. We investigated whether continuous venovenous haemofiltration, which may eliminate molecules up to 20-30 kDa, is capable of removing human leptin. Leptin measurements were made in the plasma of 15 patients with sepsis before continuous venovenous haemofiltration (T0) and during the procedure at 24 h (T1), 48 h (T2), and 72 h (T3), using samples taken before and after haemofiltration. In addition, measurements were made in the ultrafiltrate at T1-T3. The plasma leptin level at T0 was 17.6 ng mL-1. The concentration at T1 was 17.5 ng mL-1 pre-filter and 26.5 ng mL-1 post-filter (T2: 14.2/23.2 ng mL-1; T3: 12.4/16.3 ng mL-1). This concentration effect after haemofiltration was also seen with albumin. The values measured at T3 tended to be lower than those recorded at T1. The mean leptin levels in the ultrafiltrate were 0.15-0.18 ng mL-1. The range of leptin levels in the ultrafiltrate was thus only 0.5-3% of that measured in plasma. We conclude that human leptin is only minimally elimininated into the ultrafiltrate by continuous venovenous haemofiltration and that plasma leptin levels may decrease during sepsis.
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PMID:Minimal leptin elimination into ultrafiltrate during continuous venovenous haemofiltration in patients with sepsis. 1050 Sep 43

The metabolic response to critical illness promotes catabolism, which mobilizes substrates for energy. Initially the hypothalamic-pituitary-adrenal axis is stimulated, but later there appears to be anterior pituitary depression. Despite this, the early increase in plasma cortisol levels is usually maintained by means independent of (falling) corticotropin levels. Some patients, however, develop acute adrenal insufficiency and appear to benefit from replacement exogenous glucocorticoid. However, identifying such patients is often difficult. The replacement of other deficiencies may not be in the patients' interests. For example, leptin, a stress-related hormone, has multiple effects, some seemingly advantageous and others detrimental in critical illness. Its overall influence and significance remains unclear.The health of gut mucosa and the inflammatory response might be improved or influenced to the (presumed) benefit of the patient by agents such as glutamine, arginine, some eicosanoids, and exogenous nucleic acids. Such "immunonutrition" appears to improve mortality and other measures of outcome in surgical intensive care unit patients and those with sepsis.
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PMID:The metabolic and nutritional response to critical illness. 1132 6

Leptin, a cytokine involved in the regulation of food intake, has been reported to be decreased in lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis and increased in critically ill patients with sepsis. We investigated the role of leptin during hyperoxia in mice, which results in alveolar edema, severe weight loss, and death within 3-4 days. In oxygen-breathing mice, serum leptin was increased six- to sevenfold and its mRNA was upregulated in white adipose tissue. Leptin elevation could not be attributed to changes in circulating tumor necrosis factor-alpha but was completely dependent on endogenous corticosterone elevation because adrenalectomized mice did not exhibit any increase in leptin levels. Using leptin-deficient mice and wild-type mice treated with anti-leptin antibody, we demonstrate that weight loss was leptin independent. Lung damage was moderately attenuated in leptin-deficient mice but was not modified by anti-leptin antibody or leptin administration, suggesting that leptin does not play an essential role in the direct and short-term effects of oxygen-induced injury.
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PMID:Hyperoxia increases leptin production: a mechanism mediated through endogenous elevation of corticosterone. 1159 6

Despite the considerable advances made in understanding the pathophysiology of systemic inflammation during critical illness, clinical progress has been elusive as it remains a very deadly condition. Cortisol and thyroid hormone levels can be as predictive of outcome as the commonly used severity parameters (i.e. APACHE). Indeed, levels of endocrine humoral substances such as arachidonic acids, nitric oxide, endothelin, calcitonin precursors, leptin and adenosine correlate with the severity and outcome of critical illness. Furthermore, calcitonin precursors represent a potentially new hormokine paradigm, being transcriptionally activated in all cells in response to infection. The cytokines are immune markers that often correlate with severity and outcome, but their release is transient. In contrast, the so-called acute phase proteins, such as C-reactive protein and serum amyloid A, are highly sensitive to inflammatory activity and can be important markers of severity and outcome. Leukocyte esterase, adhesion molecules, platelet activating factor and activated protein C are additional humoral immune markers; the replacement of the latter has been shown to be a promising therapeutic option. Natriuretic peptides are neurocrine humoral markers that have important cardiovascular implications. The level of macrophage migrating inhibitory factor, released by the pituitary, is elevated in sepsis and counteracts glucocorticoid action. Cellular markers to severe stress include the enhanced expression of protective substances in the form of heat shock proteins. High mobility group-1 is a DNA-binding protein and a late mediator of the inflammatory response. Apoptotic markers such as the soluble fas ligand are also elevated in inflammation. In summary, during critical illness, the endocrine, immune and nervous systems elaborate a multitude of humoral markers, the roles of which merit further scrutiny in order to improve therapeutic outcome.
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PMID:Humoral markers of severity and prognosis of critical illness. 1180 May 23

Leptin, an adipocyte-derived signaling factor, is a member of the IL-6 cytokine family. However there is no direct evidence of leptin stimulation of the acute phase protein (APP) synthesis which is typical for all other IL-6-like factors. The purpose of this study was to characterize the dynamics of circulating leptin in relation to ten APPs. We used postoperative septic patients as a model of cytokine network hyperstimulation and intensive APP reaction. The prospective study was performed on 22 patients with proven postoperative intraabdominal sepsis after large abdominal surgery. Plasma levels of leptin, TNF-alpha, IL-1beta, soluble IL-2 receptor (sIL-2R), IL-6 (ELISA analysis) and ten APPs (nephelometric analysis) were estimated. We have demonstrated a statistically significant elevation of plasma leptin concentrations in the septic group compared with healthy subjects (p<0.001). The correlation of plasma leptin and BMI during postoperative sepsis was diminished. The regression coefficient was the highest for leptin and CRP (r=0.48, p<0.05), and for leptin and alpha-1-antitrypsin (r=0.46, p<0.05) in the septic group. There was significant correlation between TNF-alpha and leptin (r=0.47, p<0.05) and between IL-6 and leptin (r=0.45, p<0.05) in septic patients. No significant correlation was found between leptin and "negative" APP and between leptin and IL-1beta. Leptin has thus been shown as an acute phase reactant with a potential hematopoietic, immunomodulatory and hepatocyte stimulating activity during the infectious and non-infectious stress response. The significant correlation between leptin and CRP and leptin and alpha-1-antitrypsin indicates that leptin can participate in APP synthesis regulation during a systemic inflammatory response.
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PMID:Serum leptin levels in septic men correlate well with C-reactive protein (CRP) and TNF-alpha but not with BMI. 1182 20


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