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)

Interleukin-1 (IL-1) and interleukin-6 (IL-6), and their cognate receptors, are expressed in hippocampal neurons, which are targets for corticosteroid hormones. Corticosteroids bind to intracellular receptors, that is, mineralocorticoid (MRs) and glucocorticoid receptors (GRs). MRs respond to low concentrations of the steroid, while higher concentrations are needed for additional activation of GRs. MR occupation appears relevant in hippocampal neurons for stability of ongoing transmission, for basal activity and sensitivity of the stress response system, and for behavioural reactivity and response selection. Additional transient GR activation suppresses excitability, facilitates recovery from the stress response, and promotes information storage. Thus, the balance of MR- and GR-mediated effects appears critical for the long-term control exerted by corticosteroids over specific aspects of neuronal activity, stress responsiveness, and behavioural adaptation. Administration of IL-1 produces a long-lasting increase in corticosterone. IL-1 also influences MR function in hippocampus and causes a shift in the MR/GR balance, which may underlie prolonged activation of the HPA axis during an immune response.
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PMID:Cytokines and the brain corticosteroid receptor balance: relevance to pathophysiology of neuroendocrine-immune communication. 819 Aug 32

Interleukin-6 (IL-6), which is expressed in the human adrenal gland, was found to be a very potent activator of the human HPA axis. So far nothing is known about a local paracrine or autocrine influence of IL-6 within the human adrenal. In this study, the expression of IL-6 and the IL-6 receptor by human adrenal cells in vitro could be demonstrated by immunohistochemistry. Possible effects of IL-6 on steroid release were tested by incubating human adrenal cells in vitro with IL-6 [10(-8) M]. Adrenal steroids were stimulated by IL-6: aldosterone 184 +/- 23, cortisol 198 +/- 19, DHEA 140 +/- 8 and androstenedione 136 +/- 5 (results are means +/- s.e.m. in %). In conclusion, IL-6 can act directly on human adrenal cells and appears to be an important paracrine or autocrine factor.
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PMID:Direct effects of interleukin-6 on human adrenal cells. 896 52

The sister proteins tumor necrosis factor (TNF)-alpha and TNF-beta share 35% of their amino acid sequence and a number, but not all, of their biological properties. In the present study we infused amounts of 5 microg/kg TNF-alpha, TNF-beta (both preparations with identical bioactivities) or of solvent (0.9% sterile saline) into the circulation of guinea pigs and studied the effects on abdominal temperature, on the induction of endogenous formation of interleukin-6 and on levels of cortisol in plasma as a parameter of the activation of the hypothalamic-pituitary-adrenal axis. Infusion of TNF-alpha and TNF-beta both resulted in identical circulating TNF-like-activities corresponding to an amount of about 7000 pg/ml. TNF-alpha induced a biphasic fever lasting for more than 6 h, while in response to TNF-beta just the shorter first phase of fever (duration: 120 min) was measured. Circulating interleukin-6 (baseline level: 12-20 International Units (I.U.)/ml) and cortisol (baseline level: 70-120 ng/ml) increased about 6-fold during the first phase of the febrile response 60 min after the start of infusion with TNF-alpha or TNF-beta. Thereafter interleukin-6 and cortisol declined again in response to TNF-beta, but further increased after infusion with TNF-alpha to peak values measured 3 h after the start of infusion (interleukin-6: 258 +/- 52 I.U./ml; cortisol: 790 +/- 167 ng/ml). In animals infused with solvent abdominal temperature and interleukin-6 remained at the baseline values, just cortisol increased slightly. The results demonstrate that TNF-alpha is a much stronger inducer of fever and interleukin-6 production or of HPA-axis activation than TNF-beta in so far as all the investigated responses can be measured for prolonged time in response to TNF-alpha.
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PMID:Changes of abdominal temperature and circulating levels of cortisol and interleukin-6 in response to intra-arterial infusions of tumor necrosis factor-alpha or tumor necrosis factor-beta in guinea pigs. 936 55

Immune stimulation increases the activity of the HPA axis, a phenomenon directly or indirectly mediated through cytokines. We have used two models, the peripheral administration of endotoxin (LPS) or turpentine-induced tissue injury to show that corticotropin-releasing factor (CRF) and vasopressin (VP), hypothalamic peptides released by cytokines, play a dominant role in the increased ACTH measured in these two paradigms. In turn, CRF and VP synthesis and/or release is modulated by catecholamines, prostaglandins (PGs), and nitric oxide (NO). These secretagogues are produced in the periphery and/or the central nervous system (CNS) in response to increased cytokine levels and act on CRF/VP neurons and nerve terminals. Finally, endotoxemia and local tissue inflammation may upregulate brain levels of tumor necrosis factor alpha, interleukin-1 beta, and/or interleukin-6, providing yet another mechanism through which the occurrence of systemic inflammation is conveyed to the brain. The relative importance of brain or peripheral intermediates appears to depend on the site at which cytokine levels are increased. We have shown, for example, that peripheral, but not brain, PGs are important in mediating the neuroendocrine influence of blood-borne cytokines, while PGs in the CNS play a role in situations characterized by elevated brain immune proteins. NO, on the other hand, restrains the response of the HPA axis to circulating, but not brain cytokines. These results illustrate the complexity of the mechanisms involved in the stimulation of the HPA axis and suggest that their specific involvement depends on the type, intensity, and duration of immune stimulation.
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PMID:Mechanisms of hypothalamic-pituitary-adrenal axis stimulation by immune signals in the adult rat. 962 70

There is increasing evidence that depression and related neurotic illnesses are associated with alterations in immune function that may contribute to their pathogenesis. For example, clinical and experimental studies have shown that abnormal HPA-axis activation and monoamine neurotransmission may be related to an increased release of proinflammatory cytokines from stimulated lymphocytes in the periphery and brain. In the present investigation, the effects of tryptophan depletion (TD) on unstimulated plasma interleukin-6 (IL-6) concentrations were investigated in order to determine whether acute changes in serotonin (5-HT) neurotransmission would induce a proinflammatory response in healthy individuals. The effects of TD were compared with the analogous procedure of tyrosine depletion (TPD), which reduces catecholamine metabolism in humans. Thirteen female participants completed three experimental sessions: TD, TPD and a balanced-control condition (B). Mood-ratings and blood sampling were performed at baseline and 5 h after the administration of the mixtures. Analyses revealed that TD and TPD markedly reduced tryptophan and tyrosine/phenylalanine levels, respectively. No changes in plasma IL-6 production or ratings of lowered mood were observed, however, subjects did report feeling more fatigued after TD. These findings indicate that a transient disruption in global monoamine function does not stimulate a proinflammatory response of IL-6 in normal volunteers.
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PMID:Effects of serotonin and catecholamine depletion on interleukin-6 activation and mood in human volunteers. 1240 74

The effect of local anaesthetics on spinal nociception and activation of the hypothalamic-pituitary-adrenal axis (HPA-axis) was examined in a porcine model of abdominal surgery. A standardised laparotomy without visceral involvement was performed on 24 pigs. One group received a unilateral infiltration of mixed lidocaine and bupivacaine in skin, muscle and peritoneum of the surgical area prior to surgery (n=12), while local anaesthetics were replaced by isotonic saline in a second group (n=12). A sham group was subjected to anaesthesia (n=8), but did not undergo surgery. Two hours after surgery, half of the pigs from each group were perfused with formalin and the spinal cord was taken out for stereological quantification of the total number of Fos-like-immunoreactive (Fos-LI) neurones in the dorsal horn. Surgery with saline gave rise to a significant increase in the number of Fos-LI neurones ipsilaterally (107,001+/-16,548; p<0.001) as well as contralaterally (12,766+/-3,842; p<0.01) compared to the sham group. In animals undergoing surgery with LA, the number of Fos-LI neurones ipsilaterally was not significantly different from the sham group (p=0.78), and was reduced significantly both ipsilaterally (6960+/-1662; p<0.001) and contralaterally (3974+/-1131; p<0.05) compared to the saline group. In the other half of each group, blood samples, for determination of ACTH, cortisol, C-reactive protein and interleukin-6 concentrations, were drawn prior to and at predetermined time-points during and after surgery. Surgery with saline gave rise to dramatic increases in plasma ACTH and cortisol (p<0.01 and p<0.001, respectively) within 15 min of incision. In contrast, no changes from the initial concentrations of ACTH and cortisol were observed in pigs receiving local anaesthetics. No changes in plasma concentrations of C-reactive protein or interleukin-6 were observed in either of the groups. These results indicate that spinal nociception and HPA-axis activation caused by laparotomy in pigs can be attenuated by use of infiltration and incisional local anaesthetics prior to surgery. The present model provides a valuable tool in the evaluation of analgesic treatment during surgery, offering objective measures of both nociception and stress.
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PMID:Local anaesthetics attenuates spinal nociception and HPA-axis activation during experimental laparotomy in pigs. 1605 95

Lipopolysaccharide (LPS) induces the production of inflammatory cytokines in the serum and brain; morphine has been shown to be immunosuppressive. However, we previously reported that serum levels of LPS-induced tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) are potentiated during morphine tolerance due to the HPA axis desensitization. In this study, we examined LPS-induced cytokine production in the brain of morphine-tolerant rats. The animals were implanted with two and four morphine (75 mg) pellets on days 1 and 2, respectively. On either day 4 or 5, 250 microg/kg LPS was administered (i.p.). Animals implanted with placebo and injected with saline were used as the control. The animals were sacrificed either 16 or 2 h post-injection, respectively, and TNF-alpha, IL-1beta, and IL-6 mRNA levels in the brain were determined by reverse transcriptase polymerase chain reaction. IL-1beta mRNA increased 2 h post-LPS treatment, whereas IL-6 decreased. At 16 h, TNF-alpha expression mRNA increased. These data suggest that the inflammatory response in the brain is heightened during morphine tolerance.
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PMID:Lipopolysaccharide-induced pro-inflammatory cytokines in the brain of rats in the morphine-tolerant state. 1858 32

Although a lot is known regarding the epidemiology and aetiology of this condition, the pathophysiology of delirium remains poorly understood. Today, the leading hypothesized mechanism for the pathogenesis of delirium focuses on a central cholinergic deficiency and dopamine excess. Besides, other neurotransmitters, such as dopamine, serotonin, norepinephrine, glutamate and gamma-aminobutyric acid (GABA) may also contribute to delirium. Moreover, cytokines including interleukin-1, interleukin-2, interleukin-6, interferon and tumour necrosis factor alpha (TNF-alpha) can lead to an imbalance among the different neurotransmitters and thereby lead to an activation of the hypothalamic-pituitary-adrenocortical axis (HPA axis). The article reviews the current pathophysiological findings that may underly delirious states.
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PMID:[Delirium is a very common and life-threatening condition]. 2013 Dec 13

Research that has assessed the psychophysiological consequences of caregiver stress in young and middle aged caregivers, that is, in populations not contending with age associated decline of the endocrine and immune systems, has been scarce and yielded inconsistent findings. To extend work in this area, this study assessed the psychosocial, endocrine and immune consequences of caregiver stress in a cross sectional sample of young and middle aged caregivers of children with autism and attention deficit hyperactivity disorder (ADHD) compared against parents of typically developing children. Caregivers (n=56) and parent controls (n=22) completed measures of psychological distress (perceived stress, anxiety/depression), social support and physical health complaints. To capture important indices of the diurnal cortisol pattern, cortisol was measured at waking, 30 min post waking, 1200 h and 2200 h on two consecutive weekdays. Venous blood was taken to assess systemic concentrations of proinflammatory biomarkers, interleukin-6 (IL-6) and C-reactive protein (CRP). Caregivers scored markedly higher on all measures of psychological distress; scores on social support subscales, however, were significantly lower in this group. Diurnal patterns of cortisol secretion did not differentiate between the groups; however, caregivers displayed elevated systemic concentrations of the proinflammatory biomarker, CRP and reported more frequent episodes of physical ill health. The stress of caregiving exacts a significant psychophysiological toll, that is, even in the absence of HPA dysregulation, caregivers demonstrated elevated concentrations of proinflammatory biomarkers and, therefore, might be at greater risk for diseases fostered by disinhibition of the inflammatory response.
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PMID:The psychosocial, endocrine and immune consequences of caring for a child with autism or ADHD. 2188 67

Socioeconomic and psychosocial factors have been found to be associated with systemic inflammation. Although stress is often proposed as a contributor to these associations, no population studies have investigated the links between inflammation and biomarkers of stress. The current study examines associations between daily cortisol profiles and inflammatory markers interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor (TNF-a) in a population-based sample of 869 adults with repeat measures of cortisol over multiple days. Persons with higher levels of IL-6 had a less pronounced cortisol awakening response, a less steep daily decline, and higher cortisol area under the curve for the day with associations persisting after controls for risk factors and other cytokines. Persons with higher levels of TNF-a had lower cortisol levels upon waking, and flatter daily decline, although associations with decline were attenuated when controlling for inflammatory risk factors. Higher levels of IL-10 were associated with marginally flatter daily cortisol decline (p<.10). This study is the first to identify associations of basal cortisol activity and inflammatory markers in a population based sample. Findings are consistent with the possibility that HPA axis activity may mediate associations between psychosocial stressors and inflammatory processes. Additional prospective data are necessary to clarify the directionality of associations between cortisol and inflammatory markers.
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PMID:Associations of salivary cortisol levels with inflammatory markers: the Multi-Ethnic Study of Atherosclerosis. 2217 83


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