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Immunosuppressants, rheumatic and gastrointestinal topics
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Mechanism of action. The effects are mediated through corticosteroid receptors, members of the large steroid-nuclear receptor family that also include receptors for mineralocorticoids, sexual hormones, vitamin D, thyroid hormone and retinoic acid. The corticosteroid receptor is located in the cytoplasm and enters the nucleus of the cell after activation by different hormones. The corticosteroid receptor regulates gene transcription in target genes by binding, as a homodimer, to corticosteroid responsive elements. Corticosteroids enhance the transcription of several genes, limiting expression of inflammatory cytokines through transcription factors such as NK-kB and AP-1, associated with the induction of numerous genes, encoding for cytokines, chemokines and adhesion molecules (TNF-α, IL-1β, IL-6, ICAM-1), and resulting in the anti-inflammatory effects of corticosteroids. For some genes (IL-11, GM-CSF and cyclooxygenase), regulation of expression by corticosteroids is both transcriptional and posttranscriptional [38].
Hormones as Immune Modulating Agents
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Apparently, glucocorticoids also exert some immunoregulatory effect through the mineralocorticoid receptor (also called type I corticosteroid receptor). This receptor participated in the cortisol-induced inhibition of interleukin-1 receptor antagonist by LPS stimulated monocytes. The type I receptor antagonist spironolactone and the type II receptor antagonist RU38486 both partially reversed this inhibitory effect. Aldosterone was also inhibitory; it was blocked by spironolactone [205].
Inflammatory bowel disease
Published in Michael JG Farthing, Anne B Ballinger, Drug Therapy for Gastrointestinal and Liver Diseases, 2019
Elizabeth Carty, Anne B Ballinger
Corticosteroids are lipid-soluble and so enter target cells where they combine with cytoplasmic corticosteroid receptors. The steroid/receptor complex then translocates into the nucleus where it binds to promoter regions of several genes, which are then either activated or switched off. Corticosteroids have a wide variety of actions on cellular and humoral immune function, namely: Inhibition of leucocyte migration and activationInhibition of cytokine synthesis by suppression of the activation of the nuclear transcription factor NF kappa B (NFkB)Reduce a production of pro-inflammatory lipid mediators from arachidonic acidInhibition of phospholipase A2, cyclo-oxygenase and inducible nitric oxide synthaseStimulation of lymphocyte apoptosis in the lamina propriaEnhancement of sodium and water absorption in the gut
Female HPA axis displays heightened sensitivity to pre-pubertal stress
Published in Stress, 2020
Nichola M. Brydges, Caroline Best, Kerrie L. Thomas
Both psychological and physical stressors result in the release of corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP) from the paraventricular nucleus (PVN) of the hypothalamus. These neuropeptides act on the pituitary, stimulating the release of adrenocorticotrophic hormone (ACTH) which in turn causes the release of glucocorticoid stress hormones (corticosterone in rodents, cortisol in humans (CORT)) from the adrenal cortex (de Kloet, Joels, & Holsboer, 2005). Glucocorticoids cross the blood brain barrier and bind to corticosteroid receptors (CR: glucocorticoid (GR) and mineralocorticoid (MR) receptors) distributed throughout the brain. Feedback mechanisms then ensure the response is terminated in a healthy system. In contrast to AVP, the closely related neuropeptide oxytocin (OXT) inhibits the activity of the HPA axis (Neumann & Landgraf, 2019). HPA axis dysfunction is prevalent in psychiatric illness, for example HPA axis hyperactivity is often found in major depression and bipolar disorder, and increased or decreased HPA axis activity may be a direct consequence of ELS (Juruena, Cleare, & Young 2018; Murri et al., 2016; Zorn et al., 2017).
Oxidative stress and inflammatory response in patients with psoriasis; is there any relationship with psychiatric comorbidity and cognitive functions?
Published in Psychiatry and Clinical Psychopharmacology, 2019
Erdem Deveci, Tuba Kocacenk, Ebru Şahan, Onur Yılmaz, Ahmet Öztürk, İsmet Kırpınar
Stress exerts its effects on the immune system mainly by the hypothalamic pituitary adrenal (HPA) axis and the sympathetic adrenal medullary (SAM) axis. Psychological stress factors are processed in paraventricular nucleus of hypothalamus, afterwards produce corticotropin-releasing hormone (CRH), resulting in the secretion of corticotropin (ACTH) and cortisol. At the same time, the locus coeruleus mediates the activation of the sympathetic system causing the release of norepinephrine. Corticosteroid receptors may become insensitive to the continued effects of cortisol and the effect of catecholamines on macrophages becomes predominant. Then, the secretion of TNF-α, IL-1, and IL-6 is stimulated. Psoriatic plaques also contribute to the production of these pro-inflammatory cytokines. The effect of those cytokines on the brain induces or exacerbates symptoms of depression and re-activates the HPA axes (central and peripheral) and the sympathetic system [21].
The effects of ovarian hormones on stressor-induced hormonal responses, glucocorticoid receptor expression and translocation, and genes related to receptor signaling in adult female rats
Published in Stress, 2018
Matthew R. Green, Marina L. Marcolin, Cheryl M. McCormick
We hypothesized that estradiol would increase HPA activity and that we would see a corresponding reduction in GR expression and activity, which we assessed by measuring cytosolic and nuclear GR in the hippocampus before and after acute restraint stress. Consistent with the literature (Handa & Weiser, 2014) and with our hypothesis, ovariectomy reduced baseline and post-stress concentrations of corticosterone relative to gonadally-intact females and treatment of estradiol reversed the effect of ovariectomy. Moreover, ovariectomy increased cytosolic GR relative to several estradiol-treated groups and this group was the only one to have a stress-induced decrease in cytosolic GR, which supported our hypothesis that estradiol restricts GR expression and activity. As expected, stress increased nuclear GR expression, but contrary to our hypothesis we did not see an effect of estradiol treatment. Therefore, we found partial evidence that estradiol reduces feedback by restricting GR expression and activity. Contrary to our hypotheses, there were no differences in the expression of genes that code for corticosteroid receptors or co-chaperones and co-activators known to modulate corticosteroid receptor activity.