Stress burden and neuroendocrine regulation of cytokine production in patients with ulcerative colitis in remission
| Autor: | Laura Rebernik, Harald Engler, Jost Langhorst, Janina Köcke, Sigrid Elsenbruch, Holger Cramer, Margarita Schöls |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Male Endocrinology Diabetes and Metabolism medicine.medical_treatment Medizin Anxiety Inflammatory bowel disease Dexamethasone 0302 clinical medicine Endocrinology Glucocorticoid receptor Chronic stress Psychiatry biology Depression Middle Aged Interleukin-10 Psychiatry and Mental health Cytokine Cytokines Female medicine.symptom Lipopolysaccharide binding protein Glucocorticoid medicine.drug Signal Transduction Agonist Adult medicine.medical_specialty medicine.drug_class Inflammation 03 medical and health sciences Receptors Glucocorticoid Internal medicine medicine Humans Glucocorticoids Biological Psychiatry Endocrine and Autonomic Systems business.industry Tumor Necrosis Factor-alpha medicine.disease Neurosecretory Systems 030104 developmental biology biology.protein Quality of Life Colitis Ulcerative business 030217 neurology & neurosurgery Stress Psychological |
| Popis: | © 2018 Elsevier Ltd Stress demonstrably contributes to disease course in patients with inflammatory bowel diseases but the underlying mechanisms remain elusive. Here, we investigated if neuroendocrine regulation of pro- and anti-inflammatory cytokine production by peripheral blood immune cells is altered in patients with ulcerative colitis in remission (UCR). Using a whole blood stimulation assay, we measured the sensitivity of lipopolysaccharide (LPS)-induced TNF-α and IL-10 production to the glucocorticoid receptor agonist dexamethasone (DEX), the β 2 -adrenergic receptor agonist terbutaline (TERB), and the α7-nicotinic acetylcholine receptor agonist 3-[2,4-dimethoxy-benzylidene]-anabaseine (GTS-21) in UCR patients (N = 26) and in healthy controls (HC, N = 25). Additionally, we assessed anxiety and depression symptoms as well as chronic perceived stress and disease-specific quality of life. Results showed that UCR patients exhibited greater anxiety, depression and chronic stress levels than HC, and reduced disease-specific quality of life. Plasma concentrations of TNF-α IL-8, C-reactive protein (CRP) and lipopolysaccharide binding protein (LBP) were significantly higher, while LPS-induced IL-10 production was substantially lower in UCR compared to HC. Independent of group, DEX and GTS-21 dose-dependently inhibited TNF-α and IL-10 production, whereas TERB inhibited TNF-α and upregulated IL-10 production. However, at higher TERB doses (i.e., stress levels), upregulation of IL-10 production was significantly diminished in UCR compared to HC. Together, these findings demonstrate that downregulation of pro-inflammatory cytokine production in peripheral blood immune cells through glucocorticoid, adrenergic, and cholinergic mechanisms is essentially normal in UC in clinical remission and as efficient as in healthy individuals. However, UCR patients exhibited signs of systemic low-grade inflammation and dysregulation of anti-inflammatory IL-10 production. Impaired adrenergic upregulation of IL-10 production during remission could be one mechanism how stress facilitates relapse and conversion to symptomatic disease in these patients. |
| Databáze: | OpenAIRE |
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