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)

Prenatal exposure to benzodiazepines (BDZ) can cause behavioral dysfunctions both in humans and in experimental animals. In addition, prolonged impairment of cellular immune functions is found in rats after low dose BDZ exposure (e.g., diazepam 1.25 mg/kg/day) during part of fetal life [gestational days (GD) 14-20]. Analysis of diazepam and its metabolites in maternal and fetal tissues revealed that in this rat model the drug is no longer present at birth, which excludes direct effects of diazepam during the postnatal period. The main target of BDZ in brain, the GABAA receptor complex, is structurally and functionally heterogeneous. Besides alpha- and beta-subunits, gamma 2- or gamma 3-subunit should be coexpressed for a fully functional BDZ response. Signals of mRNAs encoding for alpha 1, beta 2 and gamma 2 are detected in fetal rat spinal cord and lower brainstem by GD 14 and reach telencephalic regions in later fetal life, reminiscent of BDZ receptor ontogeny. Regional subunit distribution differs from the adult brain, one interesting feature being a preponderance of gamma 2 mRNA throughout fetal life. Since subunit composition influences the sensitivity to BDZ, these data suggest that prenatal effects of BDZ depend upon regional subunit compositions present at different developmental stages. The delayed depression of cellular immune responses in prenatally BDZ-exposed rat offspring during the first 2 postnatal months is accompanied by various changes in immune cell biology. Binding characteristics of the peripheral (omega 3) type BDZ receptor are altered until adulthood (8 weeks). Membranes of spleen cell preparations containing mainly lymphocytes exhibit a decrease of affinity for the peripheral ligand [3H]PK11195, splenic macrophage preparations a decrease of maximal binding capacity. Various defects in cytokine production by macrophages and T lymphocytes were observed: Mitogen-stimulated release of macrophage-derived tumor necrosis factor-alpha (TNF-alpha) and of the T cell-derived interleukin-2 (IL-2) was drastically reduced at 2 and 4 weeks of life and recovered in young adulthood, exhibiting the same time course of depression as lymphocyte proliferation in response to immune stimuli. Interleukin-6 (IL-6) release remained diminished until adulthood. In female offspring, additional alterations were found in splenic noradrenaline turnover after immune stimulation. The mechanisms underlying the breakdown of the cytokine network in prenatally diazepam-exposed offspring, and the long-term consequences are as yet unknown.
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PMID:Nervous and immune systems as targets for developmental effects of benzodiazepines. A review of recent studies. 133 33

Here, we report that emotional stressors (restraint, footshock) can affect humoral immune responses as well as the capacity of immune and accessory cells to secrete interleukins. Acute restraint stress (5 min) caused a 4- to 6-fold enhancement of splenic antibody responses to sheep red blood cells. In an attempt to study endocrine mechanisms, we administered antibodies raised in rats to corticotropin releasing factor (CRF). Intravenous administration of these antibodies prior to stress-exposure and immunization prevented the stress-induced increase in the humoral response. In a parallel experiment, we observed that CRF-immunoneutralization prevented the restraint stress-induced increase in plasma ACTH concentrations, but was without effect on plasma prolactin, melanocyte stimulating hormone, adrenaline and noradrenaline responses. These data suggest the presence of an indirect pathway involving ACTH and related peptides by which CRF controls humoral responses to stress. A pathway involving a direct mechanism of CRF at the level of the immune cells will be discussed. In a set of other experiments, we addressed the question of whether interleukin-1 and interleukin-6 plasma levels induced by injection of endotoxin could be modulated by emotional stress. Exposure to prolonged footshock stress (20 min) prior to endotoxin injection resulted in a blunted plasma ACTH and interleukin-1 response, without affecting the endotoxin-induced plasma interleukin-6 response. These data suggest that at least one level at which emotional stress may influence immune function is by changing the capacity of immune cells to produce and/or secrete immune regulatory interleukins.
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PMID:Neuroendocrine and immunological mechanisms in stress-induced immunomodulation. 165 88

A 42-year-old female with high fever and headache was admitted. Physical examination revealed hypertension, thrombocytosis with megakaryocytosis, hyperfibrinogenemia, and high level of serum noradrenaline. After operation of extramedullary pheochromocytoma, all symptoms disappeared and findings became normal. The supernatant of tumor culture showed high levels of interleukin-6.
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PMID:Interleukin-6-producing pheochromocytoma. 185 86

Interleukin-6 (human recombinant) supported the survival of cultured mesencephalic, catecholaminergic and septal cholinergic neurons from postnatal, two-week-old (P13-P15) rats. Significantly, more catecholaminergic neurons, stained by monoclonal anti-tyrosine hydroxylase antibody, were found in cultures supplemented with interleukin-6 at a concentration of 5 ng/ml than in cultures not treated with interleukin-6. The optimal dose used was 50 ng/ml. The survival effect of interleukin-6 on postnatal rat, tyrosine hydroxylase-positive neurons was observed both in cultures using serum-containing and serum-free medium. Contents of dopamine and noradrenaline in cultures with interleukin-6 were also larger than in control cultures. Interleukin-6 also increased the survival of cultured embryonic (E17) rat midbrain tyrosine hydroxylase-positive neurons. The effect on these neurons was, however, smaller, and the optimal dose of interleukin-6 was nearly 5 ng/ml. Interleukin-6 also supported the survival of cultured postnatal (P13) rat septal cholinergic neurons, visualized by acetylcholinesterase staining. The concomitant addition of mouse nerve growth factor (100 ng/ml) and interleukin-6 (50 ng/ml) had a synergetic effect on the survival of acetylcholinesterase-positive neurons in culture. Our data suggest that the survival of cultured tyrosine hydroxylase-positive, mesencephalic, and acetylcholinesterase-positive, septal neurons from postnatal two-week-old rats was supported by interleukin-6, just as there was a different dose dependency of interleukin-6 on the cultured postnatal neurons compared with embryonic neurons.
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PMID:Interleukin-6 improves the survival of mesencephalic catecholaminergic and septal cholinergic neurons from postnatal, two-week-old rats in cultures. 202 69

In animal models authors have dealt with the question of whether hypotension alone can cause an acute-phase response even in the absence of marked blood loss and trauma. Sodium nitroprusside (SNP), which was employed in the animal models, is also used to induce hypotension in humans. Since no data are available on human subjects plasma concentrations of interleukin-6 (IL-6), an important mediator of the acute-phase response, were studied in patients during SNP infusion for induction of hypotension. METHODS. After approval by the local ethics committee, 20 patients scheduled for elective oto-rhino-laryngological operations participated in this randomised prospective study. Anaesthesia was induced with fentanyl, etomidate, vecuronium and succinylcholine and was maintained with isoflurane in 66% N2O and 33% O2. Ten patients received SNP to reduce mean arterial blood pressure to 50 mmHg, while another ten patients served as controls. Blood samples were taken before the induction of anaesthesia, during surgery (at the end of the SNP infusion), 60 min after surgery and on the day after surgery. IL-6 concentrations were determined by means of enzyme-linked immunosorbent assay. Epinephrine and norepinephrine in plasma were measured by high-pressure liquid chromatography with electrochemical detection. RESULTS. The IL-6 plasma concentration increased significantly from 3.2 (0-7.5) pg/ml (median and range) to 31.8 (9-42.2) pg/ml in the SNP group and from 3.5 (0-8.3) pg/ml to 15.2 (7.4-19) pg/ml in the control group on the morning after surgery. The IL-6 values at this time were significantly (P < 0.05) higher in the SNP group than in the controls. Norepinephrine increased significantly from 263 (150-920) pg/ml (median and range) preoperatively to 419 (115-897) pg/ml, and the epinephrine concentrations rose significantly from 77 (12-159) pg/ml to 115 (83-330) pg/ml at the end of SNP administration. No significant changes in the catecholamine concentrations were observed in the control group. CONCLUSIONS. The SNP infusion exerted an important additional stimulus for IL-6 release after relatively mild surgical trauma in both groups. This finding is probably due to the liberation of NO from the SNP molecule and an increase in the intracellular concentration of cGMP. The elevation of the plasma catecholamines immediately after SNP administration should also be taken into account, because an augmentation of the cAMP in various cell types has been proven to result in increased release of IL-6.
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PMID:[Increase in interleukin-6 plasma concentrations following hypotensive anesthesia with sodium nitroprusside]. 761 79

The effect of selective block of alpha 2-adrenoreceptors on plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and corticosterone induced by bacterial lipopolysaccharide (LPS) was investigated in mice using ELISA and RIA. It was found that the LPS-induced TNF-alpha response was significantly blunted in mice pretreated with CH-38083, a novel and highly selective alpha 2-adrenoreceptor antagonist (the alpha 2/alpha 1 ratio is > 2000). In contrast, LPS-induced increases in both corticosterone and IL-6 plasma levels were further increased by CH-38083. Since it has recently been shown that the selective block of alpha 2-adrenoreceptors located on noradrenergic axon terminals resulted in an increase in the release of noradrenaline (NA), both in the central and peripheral nervous systems, and, in our experiments, that propranolol prevented the effect of alpha 2-adrenoreceptor blockade on TNF-alpha plasma levels induced by LPS, it seems likely that the excessive stimulation by NA of beta-adrenoreceptors located on cytokine-secreting immune cells is responsible for this action. Since it is generally accepted that increased production of TNF-alpha is involved in the pathogenesis of inflammation and endotoxin shock on the one hand, and corticosterone and even IL-6 are known to possess anti-inflammatory properties on the other hand, it is suggested that the selective block of alpha 2-adrenoreceptors might be beneficial in the treatment of inflammation and/or endotoxin shock.
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PMID:Differential effect of selective block of alpha 2-adrenoreceptors on plasma levels of tumour necrosis factor-alpha, interleukin-6 and corticosterone induced by bacterial lipopolysaccharide in mice. 773 70

Resident glial cells and invading inflammatory cells are responsible for cytokine production within the brain. Astrocytes are known to secrete a variety of cytokines upon stimulation with cytokines themselves, protein kinase C activators, bacterial or viral constituents. Astrocytes also have surface receptors for a wide number of neurotransmitters and neuropeptides and some of these substances affect astrocyte immune functions, such as major histocompatibility complex (MHC) class II antigen expression. To elucidate the activity of neuromediators on cytokine secretion by glial cells, we studied the secretion of interleukin-6 (IL-6) by cultured rat astrocytes after incubation with various neurotransmitters and neuropeptides. Norepinephrine (NE) and the beta-adrenergic agonist isoproterenol (IPT) induced IL-6 secretion in a dose-dependent fashion. NE effect was predominantly mediated by beta 2-adrenergic receptors with a minor contribution of alpha 1-adrenergic receptors. The induction of IL-6 release by dibutyryl-cAMP indicated that IL-6 secretion secondary to beta 2-adrenergic receptor activation probably occurs through cAMP signalling pathways. Vasoactive intestinal peptide (VIP) was the sole neuropeptide able to induce IL-6 secretion. NE and VIP promoted IL-6 mRNA synthesis and both substances synergized with interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) in inducing IL-6 release. Our findings provide further evidence that neurons modulate astrocyte cytokine production and thereby regulate central nervous system immune functions.
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PMID:Norepinephrine and vasoactive intestinal peptide induce IL-6 secretion by astrocytes: synergism with IL-1 beta and TNF alpha. 837 50

In the present study, we have investigated the ability of four cytokines, interleukin-1 beta, interleukin-2, interleukin-6 and tumor necrosis factor-alpha, to modulate the stimulation-induced outflow of radioactivity from isolated superfused mouse atria which where pre-incubated with [3H]-noradrenaline. The tissues were subjected twice to field stimulation (5 Hz frequency, 50 mA intensity, 2 ms pulses for 60 s) and the drugs were added prior to the second stimulation in order to assess their modulatory effects. The results show that mouse recombinant interleukin-1 beta and tumor necrosis factor-alpha inhibited the stimulation-induced release of radioactivity from the isolated mouse atria. The effect of interleukin-1 beta was blocked by a human recombinant interleukin-1 receptor antagonist. The inhibitory effect of interleukin-1 beta was also abolished by the cyclooxygenase inhibitor, diclofenac (1 mumol/l) suggesting that the action of interleukin-1 beta might be mediated through the formation of prostaglandins. The effect of interleukin-1 beta appears to be time-dependent, since a stronger inhibition of radio-activity release was observed when the incubation time was increased from 20 to 65 minutes before the second stimulation. Interleukin-2 and interleukin-6 were ineffective in modulating release under these experimental conditions. The ability of interleukin-1 beta and tumor necrosis factor-alpha to inhibit noradrenaline release suggests that mediators of the immune system produced locally may modulate the activity of the sympathetic nervous system.
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PMID:Interleukin-1 beta and tumor necrosis factor-alpha inhibit the release of [3H]-noradrenaline from mice isolated atria. 883 81

Acute muscular exercise induces an increased neutrophil count concomitant with recruitment of natural killer (NK), B and T cells to the blood as reflected by an elevation in the total lymphocyte count. Meanwhile, following intense exercise of long duration the lymphocyte count declines, non-MHC-restricted cytotoxicity is suppressed, but the neutrophil concentration increases. In relation to eccentric exercise involving muscle damage, the plasma concentrations of interleukin-1, interleukin-6 and the tumor necrosis factor are elevated. In this review we will propose a model based on the possible roles that stress hormones play a mediating the exercise- related immunological changes: adrenaline and to a lesser degree noradrenaline are responsible for the immediate effects of exercise on lymphocyte subpopulations and cytotoxic activities. The increase in catecholamines and growth hormone mediate the acute effects of exercise on neutrophils, whereas cortisol may be responsible for maintaining lymphopenia and neutrocytosis after exercise of long duration. Lastly, the role of beta-endorphin is less clear, but the cytokine response is closely related to muscle damage and stress hormones do not seem to be directly involved in the elevated cytokine level. Other possible mechanisms of exercise-induced immunomodulation may include the so-called glutamine hypothesis, which is based on the fact that skeletal muscle is an important source of glutamine production and that lymphocytes are dependent on glutamine for optimal growth. Furthermore, physiological changes during exercise, e.g. increased body temperature and decreased oxygen saturation may also in theory contribute to the exercise-induced immunological changes.
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PMID:Exercise-induced immunomodulation--possible roles of neuroendocrine and metabolic factors. 912 58

To study the role of the sympathetic nervous system in the induction of inflammatory cytokines elicited by central lipopolysaccharide, sympathetic chemical denervation was performed by intraperitoneal injection of 6-hydroxydopamine. Rats received the neurotoxin according to the following schedule: 50 mg/kg on days 1 and 2, 100 mg/kg on days 3, 4 and 7. On day 8, lipopolysaccharide (2.5 microg/6 microl/rat) was injected intracerebroventricularly and rats were killed 2 h later. 6-Hydroxydopamine reduced noradrenaline and dopamine content in the spleen by 88.7% and 88.8% respectively, without affecting striatal contents indicating that the chemical sympathectomy had been effective and selective. In sympathectomized rats, lipopolysaccharide raised interleukin-1beta and interleukin-6 serum levels more than in control rats given the vehicle. Tumour necrosis factor-alpha serum levels in sympathectomized rats were no different from those in vehicle-treated rats. Interleukin-1beta and interleukin-6 messenger RNA expression, measured by northern blot analysis, was clearly detectable in adrenals and spleen of rats given lipopolysaccharide. Sympathectomy increased lipopolysaccharide-induced interleukin-1beta and interleukin-6 messenger RNA in adrenals and spleen. Corticosterone basal levels were raised by central lipopolysaccharide and not further changed by sympathectomy. The present study shows that sympathetic nervous system denervation enhances the synthesis and production of peripheral interleukin-1beta and interleukin-6 in rats given central lipopolysaccharide and suggests a tonic inhibitory control of the sympathetic nervous system on these inflammatory cytokines.
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PMID:The sympathetic nervous system tonically inhibits peripheral interleukin-1beta and interleukin-6 induction by central lipopolysaccharide. 950 62


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