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)

Metallothionein (MT), a low molecular-weight, cysteine-rich, metal-binding protein, is induced by many environmental factors and a variety of stimuli. Bacterial endotoxin (lipopolysaccharide, LPS) injection is experimentally used to produce acute stress and is an effective inducer of hepatic MT. However, the mechanism of LPS induction of MT is not known. In the present studies, we used two substrains of mice, differing in their production of cytokines after LPS administration, to test the hypothesis that MT induction by LPS is mediated through cytokines. Normal (C3Heb/FeJ) and low cytokine-producing (C3H/HeJ) mice were given various doses of LPS, interleukin-1 (IL-1), interleukin-6 (IL-6), or tumor necrosis factor (TNF), and hepatic MT was determined 24 hr later by the Cd/hemoglobin assay. The low-cytokine-producing mice were much less responsive to the induction of MT by LPS (50 vs 150 micrograms MT/g liver after 1.0 mg LPS/kg, ip) than the normal mice, but were equally responsive to the induction of MT by IL-1 (0.03-1.0 microgram/mouse). IL-6 (0.5-5.0 micrograms/mouse), and TNF (0.005-0.5 microgram/mouse). All the cytokines produced a dose-dependent increase of hepatic MT levels in these two murine substrains (up to five- to sevenfold over controls). In conclusion, these data suggest that LPS induction of MT may be mediated through cytokines.
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PMID:Endotoxin induction of hepatic metallothionein is mediated through cytokines. 206 24

Acute release of corticotropin-releasing factor (CRF) during repeated restraint (3-h restraint on each of 3 days) causes temporary hypophagia but chronic suppression of body weight in rats. Here we demonstrated that a second bout of repeated restraint caused additional weight loss, but continuing restraint daily for 10 days did not increase weight loss because the rats adapted to the stress. In these two studies serum leptin, which suppresses the endocrine response to stress, was reduced in restrained rats. Peripheral infusion of leptin before and during restraint did not prevent stress-induced weight loss, although stress-induced corticosterone release was suppressed. Restrained rats were hyperthermic during restraint, but there was no evidence that fever or elevated free interleukin-6 caused the sustained reduction in weight. Restraining food-restricted rats caused a small but significant weight loss. Food-restricted rats fed ad libitum after the end of restraint showed a blunted hyperphagia and slower rate of weight regain than their controls. These results indicate that repeated acute stress induces a chronic change in weight independent of stress-induced hypophagia and may represent a change in homeostasis initiated by repeated acute activation of the central CRF system.
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PMID:Weight loss in rats exposed to repeated acute restraint stress is independent of energy or leptin status. 1174 26

Glucocorticoids can down-regulate immune activity, but acute stress has been reported to increase both cortisol and levels of plasma cytokines. We investigated individual differences in cortisol responses and their associations with proinflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), cardiovascular activity, and mental health. Saliva samples and blood were taken from 199 healthy middle-aged participants of the Whitehall II cohort at baseline, immediately after stress and 45 min later. We defined the 40% of participants with the highest cortisol response to stress as the cortisol responder group and 40% with the lowest response as the cortisol non-responder group. Plasma IL-6 was higher and the IL-1ra response to stress was greater in the cortisol non-responder group. The cortisol non-responders showed lower heart rate variability than the cortisol responders. The cortisol responder group experienced more subjective stress during the tasks and reported more impaired mental health than the non-responders. We conclude that individual variations in neuroendocrine stress responsivity may have an impact on proinflammatory cytokines, and that both high and low cortisol stress responsiveness has potentially adverse effects.
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PMID:Cortisol responses to mild psychological stress are inversely associated with proinflammatory cytokines. 1294 59

Effects of three experimental manipulations: mental stress, relaxation, and a nociceptive inflammatory stimulus, capsaicin, on levels of interleukin-6 (IL-6) were examined. Fifty subjects were pre-trained in relaxation and then randomized to a stress (Stroop test), relaxation (tape), or control (video) manipulation. Subjects participated in an evening reactivity session including 20 min of stress, relaxation, or control followed by a capsaicin injection in the forearm. Cardiovascular variables and levels of IL-6 were measured before and after the manipulation, and at regular intervals up to 60 min post-capsaicin. Group assignment did not differentially affect change in IL-6 over time, either before or after capsaicin. Small but significant increases in IL-6 were seen at 60 min post-capsaicin. These findings suggest that an acute stress manipulation does not modulate IL-6 within this time frame. Although IL-6 did increase following a neurogenic inflammatory stimulus, it did so subsequent to the maximum flare, suggesting that flare mechanisms are independent of IL-6.
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PMID:Effects of acute stress, relaxation, and a neurogenic inflammatory stimulus on interleukin-6 in humans. 1465 47

The role of cytokines in depression was first considered when the cytokine interferon resulted in "sickness behaviour", the symptoms of which are similar to those of major depression. The latter is associated with an increase in pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha). These cytokines are potent modulators of corticotropin-releasing hormone (CRH) which produces heightened hypothalamic-pituitary-adrenal axis (HPA) activity characterized by increases in ACTH and cortisol, both of which are reported elevated in major depression. Antidepressant treatment has immunomodulatory effects with increases in the production of IL-10, which is an anti-inflammatory cytokine. This review based on a Medline search from 1980-2003, focuses on the evidence available of cytokine changes in acute stress, chronic stress and major depression. It examines the effects of antidepressant treatment on immune parameters in both animal models and clinical trials. We suggest that future antidepressants may target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.
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PMID:Cytokines: abnormalities in major depression and implications for pharmacological treatment. 1530 43

Animal studies have shown that an acute stressor in close temporal proximity to immune challenge can enhance the response to delayed-type hypersensitivity and antibody response to vaccination. The current study examined the effects of acute exercise or mental stress prior to influenza vaccination on the subsequent antibody response to each of the three viral strains. Sixty young healthy adults (31 men, 29 women) were randomly allocated to one of three task conditions: dynamic exercise, mental stress, or control. After an initial baseline, participants completed their allocated 45 min task and then received the influenza vaccine. Plasma cortisol and interleukin-6 were determined at the end of baseline, after the task, and after 60 min recovery. Antibody titres were measured pre-vaccination and at 4 weeks and 20 weeks post-vaccination follow-ups. For the A/Panama strain, women in both the exercise and mental stress conditions showed higher antibody titres at both 4 and 20 weeks than those in the control condition, while men responded similarly in all conditions. Interleukin-6 at +60 min recovery was found to be a significant predictor of subsequent A/Panama antibody response in women. In line with animal research, the current study provides preliminary evidence that acute stress can enhance the antibody response to vaccination in humans.
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PMID:Acute stress exposure prior to influenza vaccination enhances antibody response in women. 1610 36

Changes in brain tryptophan concentrations may affect the synthesis of brain serotonin (5-hydroxytryptamine, 5-HT). Concentrations of tryptophan are regulated more than those of any other amino acid. Such stimuli as acute stress, carbohydrate ingestion, and treatment with various drugs increase the brain content of tryptophan. Treatment of rats and mice with interleukin-1 (IL-1), interleukin-6 (IL-6), lipopolysaccharide (LPS), and beta-adrenoceptor agonists, as well as a variety of stressors, such as footshock and restraint, all increase brain concentrations of tryptophan. The peak effect following both acute stress and beta-adrenoceptor agonist administration occurs within 30-60 min, whereas the peak effect following LPS and the cytokines occurs much later at around 4-8 h. Experiments using the ganglionic blocker chlorisondamine, and beta-adrenoceptor antagonists suggest that the sympathetic nervous system plays an important role in the modulation of brain tryptophan concentrations. The mechanisms involved in the increases observed in brain tryptophan are discussed, as well as their possible biological significance.
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PMID:Mechanisms and significance of the increased brain uptake of tryptophan. 1636 73

We have analyzed in molecular detail how soy isoflavones (genistein, daidzein, and biochanin A) suppress nuclear factor-kappaB (NF-kappaB)-driven interleukin-6 (IL6) expression. In addition to its physiologic immune function as an acute stress cytokine, sustained elevated expression levels of IL6 promote chronic inflammatory disorders, aging frailty, and tumorigenesis. Our results in estrogen-unresponsive fibroblasts, mitogen- and stress-activated protein kinase (MSK) knockout cells, and estrogen receptor (ER)-deficient breast tumor cells show that phytoestrogenic isoflavones can selectively block nuclear NF-kappaB transactivation of specific target genes (in particular IL6), independently of their estrogenic activity. This occurs via attenuation of mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK) and ERK activity, which further down-regulates MSK-dependent NF-kappaB p65 and histone H3 phosphorylation. As constitutive NF-kappaB and MSK activity are hallmarks of aggressive metastatic ER-deficient breast cancer, the MSK signaling pathway may become an attractive target for chemotherapy.
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PMID:Attenuation of mitogen- and stress-activated protein kinase-1-driven nuclear factor-kappaB gene expression by soy isoflavones does not require estrogenic activity. 1665 41

The present study investigated the possibility that acute stress might activate microglial cells. Wistar rats were exposed to 2 h period of restraint combined with water immersion stress prior to brain analysis by immunohistochemistry with OX-42, a marker of complement receptor CR3. A single session of stress provoked robust morphological microglial activation in the thalamus, hypothalamus, hippocampus, substantia nigra and central gray. These effects appeared as early as at 1 h of exposure and were further intensified at 2 h. Morphological activation was not accompanied with changes in markers of functional activation or of inflammation including interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS). Similar results were obtained with mice where the effects of stress were compared in animals null for interleukin-18 (IL-18 KO), a cytokine previously demonstrated to be modulated by stress and to contribute to microglia activation. The results demonstrated significant reduction of stress-induced microglial activation in IL-18 KO mice. The present study reports evidence that physical/emotional stress may induce morphological microglial activation in the brain and this activation is in part mediated by interleukin-18.
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PMID:Stress induced morphological microglial activation in the rodent brain: involvement of interleukin-18. 1743 55

Acute mental stress tests have helped to clarify the pathways through which psychosocial factors are linked to disease risk. This methodology is now being used to investigate potentially protective psychosocial factors. We investigated whether global self-esteem might buffer cardiovascular and inflammatory responses to acute stress. One hundred and one students completed the Rosenberg Self-Esteem Scale. Heart rate and heart rate variability (HRV) were recorded for 5 min periods at baseline, during two mental stress tasks, (a speech and a color-word task) and 10, 25 and 40 min into a recovery period. Plasma levels of tumor-necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1Ra) were assessed at baseline, immediately post-stress and after 45 min recovery. Repeated measures analysis of variance demonstrated that heart rate levels were lower across all time points in those with high self-esteem, although heart rate reactivity to stress was not related to self-esteem. There were no differences in baseline HRV, TNF-alpha, IL-6 or IL-1Ra. Multiple linear regressions revealed that greater self-esteem was associated with a smaller reduction in heart rate variability during the speech task, but not the color-word task. Greater self-esteem was associated with smaller TNF-alpha and IL-1Ra responses immediately following acute stress and smaller IL-1Ra responses at 45 min post-stress. In conclusion, global self-esteem is associated with lower heart rate and attenuated HRV and inflammatory responses to acute stress. These responses could be processes through which self-esteem protects against the development of disease.
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PMID:Self-esteem levels and cardiovascular and inflammatory responses to acute stress. 1864 32


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