Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Corticotropin-releasing hormone (CRH) was initially sequenced and identified in 1981, and has since become established as the principal organizer of the stress response. It causes activation of the pituitary-adrenal axis, behavioural arousal, sympathetic stimulation and a decrease in appetite. In vitro studies have shown regulation of hypothalamic CRH by a variety of neuro-transmitters, including the cytokines interleukin-1 and interleukin-6. However, circulating CRH is mainly derived from extra-hypothalamic sites, and levels may be elevated in patients with tumours secreting ectopic CRH. The placenta is a further source of CRH, which may be specifically raised in patients with pre-eclampsia, and could be a factor in the initiation of parturition. The recently identified CRH binding protein may play a vital role in this process. Clinically, CRH testing has become extremely useful in the diagnosis and differential diagnosis of Cushing's syndrome, and particularly for the localization of ACTH following inferior petrosal sinus catheterization. There is considerable evidence that many patients with depressive illness may have a disturbance of the central control of CRH, and this may be become of increasing importance in the therapy of this common condition. There are also intriguing new data suggesting that abnormalities in CRH regulation may be involved in the pathogenesis of inflammatory arthritis.
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PMID:Corticotropin-releasing hormone in health and disease: an update. 141 42

Patients with hypertensive disorders of pregnancy demonstrated higher neopterin/creatinine ratios (urine) and elevated plasma levels of interleukin-6, tumor necrosis factor alpha and neopterin. A participation of macrophages in the pathomechanism of preeclampsia can thus be assumed.
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PMID:[Activated macrophages in the pathologic mechanism of pregnancy-induced hypertension]. 802 23

1H spin echo NMR was used to follow the release of reactive oxygen species (ROS) from human monocytes by monitoring erythrocyte glutathione status, which is sensitive to applied oxidative stress. This allowed the ability of the cytokine interleukin-6 (IL-6) to stimulate release of ROS from monocytes to be assessed in terms of oxidative damage to other cells, providing an estimation of its importance in vivo. It was found that incubation of monocytes with erythrocytes in the presence of IL-6 resulted in oxidation of the erythrocyte glutathione pool, indicating that oxidants are released in sufficient amounts to cause oxidative stress. High levels of IL-6 occurring in plasma of women with severe pre-eclampsia could therefore be responsible for depleted plasma antioxidants and haemolysis. The oxidation of erythrocyte glutathione was inhibited by the presence of the cyclooxygenase inhibitor indomethacin, suggesting that this may be of value in the treatment of oxidative pathologies.
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PMID:Oxidation of erythrocyte glutathione by monocytes stimulated with interleukin-6. Analysis by 1H spin echo NMR. 954 49

Endothelial injury is common to all pathological features of preeclampsia. Neutrophil activation has been implicated in the pathophysiology of preeclampsia and requires binding and transmigration of neutrophils through the endothelium. This occurs via an interaction of endothelial adhesion molecules and surface receptors on neutrophils. Upon activation, neutrophil granules are released, the contents of which are capable of mediating vascular damage. In addition, leukotrienes are synthesized, and superoxide is generated in a respiratory burst. These products also provoke vascular damage. Neutrophil recruitment to the endothelium involves express of P-selectin and released of platelet activating factor from the endothelium. In preeclampsia there is evidence of an increase in neutrophil activation with up-regulation of neutrophil integrin expression and increased regulation of the protease elastase. Furthermore, these markers of neutrophil activation correlate with established markers of disease severity. The primary mechanism of neutrophil activation is unknown, but neutrophils in preeclampsia appear to have normal motor activity. Several potential mechanisms of neutrophil activation have been identified. They include up-regulation of cellular adhesion molecules on the endothelial surface, increased generation of tumor necrosis factor-alpha, and endothelial activation from hyperlipidemia. In additional to activation of neutrophils in preeclampsia, there may be involvement of the interleukin-6 and endothelin-1 in "priming" neutrophils for subsequent superoxide production. Activated neutrophils are likely to play a large part in the arteriopathy and endothelial damage associated with preeclampsia, but it is unclear whether neutrophil activation is the cause or the consequence of endothelial damage.
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PMID:The neutrophil and preeclampsia. 965 8

In this study we evaluated the maternal cell-mediated immune aspects of preeclampsia in terms of phagocytosis and killing of monocytes and polymorphonuclear cells. To evaluate the contribution of cytokines (Cks) in the pathophysiology of preeclampsia, we investigated the plasma levels of interferon-gamma (IFN-gamma), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), respectively, by an enzyme-linked immunosorbent assay. Data showed that phagocytic and killing activities of monocytes were depressed in preeclamptic and normal pregnancies. At the same time, IFN-gamma plasma levels were undectable in both groups. Conversely, we detected significant levels of TNF-alpha in plasma from preeclamptic and normal pregnancies. Moreover, since in three preeclamptic patients the onset of severe preeclampsia was associated with a sharp increased of TNF-alpha plasma levels, we suggest that an increased production of this CK may be implicated in the pathophysiology of preeclampsia.
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PMID:Evaluation of nonspecific immunity and plasma levels of interferon-gamma, interleukin-6 and tumor necrosis factor-alpha in preeclampsia. 1046 79

It is possible that in fetal growth restriction without pre-eclampsia endothelial cell activation does not occur. This might be either because there is no release of 'factor X' or because of maternal resistance to its effects. To test this hypothesis, we took blood samples from 26 women with pre-eclampsia (without fetal growth restriction), 13 women with fetal growth restriction (without pre-eclampsia) and 24 normal pregnant controls, and measured the circulating levels of three markers of endothelial cell activation (soluble VCAM, ICAM and E-selectin) and three cytokines [tumour necrosis factor-a (TNF-alpha), interleukin-6 (IL-6) and -8 (IL-8)]. The levels of the markers of endothelial cell activation were raised in both pre-eclampsia and fetal growth restriction pregnancies compared with controls; however, the levels of TNF-alpha, IL-6 and IL-8 were significantly raised in pregnancies complicated by pre-eclampsia, but not in fetal growth restriction, compared with controls. These data show that endothelial cell activation is common to both pre-eclampsia and fetal growth restriction, but that the circulating levels of cytokines are elevated only in pre-eclampsia. Thus, it seems likely that endothelial cell activation is a consequence of a failure of trophoblast invasion and that a further step is required, possibly involving cytokine release, for the expression of the full clinical picture of pre-eclampsia.
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PMID:Does endothelial cell activation occur with intrauterine growth restriction? 1213 23

Sudden infant death syndrome (SIDS) or crib or cot death are synonyms for the sudden, unexpected and unexplained death of an infant. The incidence of SIDS has been estimated to be from 1-2% to 3%. Protracted intrauterine hypoxia or recurrent hypoxic insults during fetal life undoubtedly influence the development of the central nervous structures as a tissue most susceptible to hypoxia, although well developed mechanisms of defense against hypoxia exist during the fetal life. The mechanisms underlying SIDS include neurologically compromised infants who are deprived of compensatory mechanisms during sleep, sustaining a hypoxic insult with alterations in neurotransmitter receptors within the regions involved in chemoreception and cardiovascular control. Changes in the brain result from perinatal prolonged hypoxia (persistent reticular pathways in the pons and medulla, astroglia in the brainstem, gliosis of brain nerve nuclei, defects in neurotransmitter receptors, neuronal apoptosis, microthrombosis, and hypoxic ischemic lesion). Hypoxic perinatal risk factors for SIDS included passive and active exposure to cigarette smoking in pregnancy, abuse of drugs, alcohol, coffee and medication in pregnancy, intrauterine growth retardation, perinatal hypoxia with or without resuscitation, preeclampsia, anemia in pregnancy, prematurity, multiparity, multiple pregnancy, pregnant women aged < 20 years and > 35 years, cardiocirculatory, pulmonary and endocrine diseases in pregnancy, and short time interval between two pregnancies. As cigarette smoking has been demonstrated to lead to fetoplacental insufficiency, which result in fetal hypoxia, it is concluded that hypoxia is a precondition for the occurrence of SIDS. Prenatal exposure to cigarette smoke decreases maternal red blood cell count, and concentrations of tyrosine and selenium, reduces fetal and neonatal cerebral blood flow, and increases maternal MCV, leukocytosis, especially neutrophils, monocytes and lymphocytes, maternal and fetal heart rate, systolic and diastolic blood pressure, resistance index in umbilical artery, fetal hemoglobin, cytokine, serotonine, dopamine, catecholamine, hypoxanthine, endorphin and interleukin-6. Pregnancy at a risk of hypoxia, especially in heavy smokers, is a major risk factor for SIDS, and such pregnancy requires close and intensive antenatal monitoring.
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PMID:[Intrauterine hypoxia and sudden infant death syndrome]. 1263 Mar 42

Both insulin resistance and inflammation may contribute to the onset of preeclampsia. They also could be interrelated. We studied the relationship between inflammatory cytokines and markers of insulin resistance. During their third trimester, 22 proteinuric preeclamptic women and 16 normotensive controls underwent intravenous glucose tolerance test (minimal model). Preeclamptic women were more insulin-resistant (P = .009), and they had higher levels of serum soluble tumor necrosis alpha receptor II (TNFalpha RII) (P = .002), triglycerides (P = .006), uric acid (P = .001), and leptin (P = .002) than did the controls. However, the study groups did not differ in serum TNFalpha, C-reactive protein (CRP), interleukin-6 (IL-6), sex hormone-binding globulin (SHBG), and high-density lipoprotein-2 (HDL(2))-cholesterol. In multiple regression analysis only SHBG (P = .01) and triglycerides (P = .0036) were associated with insulin sensitivity independently of body mass index (BMI), weight gain, HDL(2)-cholesterol, CRP, TNFalpha, and TNFalpha RII, IL-6, and leptin. We conclude that insulin resistance and the inflammatory markers studied were not associated in established preeclampsia.
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PMID:Is there any link between insulin resistance and inflammation in established preeclampsia? 1553 97

Observations that the innate arm of the immune system is upregulated in pregnancy have highlighted the need for methods of isolating pure populations of monocytes for studies into pregnancy and pre-eclampsia without activating them during the isolation process. Density gradient centrifugation using iodixanol is a useful method for isolating relatively pure populations of unactivated monocytes from human blood but has not been validated in pregnant subjects. We compared the ability of monocytes isolated from pregnant women by density gradient centrifugation using iodixanol (n=6) with monocytes isolated by countercurrent centrifugal elutriation (n=6) in terms of their ability to produce interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) under basal conditions and after stimulation with bacterial lipopolysaccharide (LPS). Under basal conditions, monocytes isolated by density gradient centrifugation produced low amounts of IL-6 and MCP-1. Production of IL-6 and MCP-1 after stimulation of the monocytes with LPS was much greater (p<0.01). There was no statistically significant difference between the two methods in terms of stimulated levels of either cytokine.
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PMID:Isolating pure populations of monocytes from the blood of pregnant women: comparison of flotation in iodixanol with elutriation. 1554 Dec 90

Preeclampsia is a multisystem disorder manifest by hypertension after 20 weeks' gestation associated with end organ damage, usually proteinuria. The placenta is thought to be pivotal in the pathogenesis of the disease. Both the placenta and the maternal systemic response are characterised by heightened inflammation. Garlic has been shown to have anti-inflammatory and pro-apoptotic properties amongst others. It was hypothesised that treating placental explants with garlic may inhibit the production of inflammatory cytokines (interleukin-6 (IL-6) and tumour necrosis factor (TNFalpha)) and stimulate the production of anti-inflammatory cytokines (interleukin-10 (IL-10)) by the placental explants. Garlic, we hypothesised, would also stimulate apoptosis in the explants as measured by soluble TNF-related apoptosis-inducing ligand/Apo-2L (sTRAIL) production. Normal placental explants (n=5) and explants from women who had preeclampsia (n=4) were cultured in the presence of various garlic concentrations (10-1000 microg/mL). The lowest garlic concentration (10 microg/mL) increased the normal explant production of IL-10 by 29.2% (12.2, 57.5%; p<0.01) while inhibiting the production of IL-6 by 23.5% (8.9, 32.5%; p<0.01) (normal explants) and TNFalpha by 19.4% (4.5, 35.3%; p<0.05) (preeclamptic explants). Garlic resulted in an increase in IL-10 production at lower doses (normal explants only) and inhibition of the production of IL-10 at higher doses (normal and preeclamptic explants). Garlic also resulted in a dose-dependent reduction of IL-6 and TNFalpha. Initially there was no change in sTRAIL production; however, at the highest garlic concentrations there was a significant increase in production. We thus conclude that garlic may have an immunomodulatory effect on normal and preeclamptic placentas.
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PMID:Garlic increases IL-10 and inhibits TNFalpha and IL-6 production in endotoxin-stimulated human placental explants. 1622 32


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