Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vagotomy suppresses fever and hyperalgesia caused by intraperitoneal lipopolysaccharide (LPS) but has little effect on the febrile response to intravenous or intramuscular LPS. This suggests that some vagus-mediated mechanisms are recruited only when LPS is administered via the intraperitoneal route. We hypothesized that such mechanisms are associated with LPS transport from the peritoneal cavity to the circulation. Adult Wistar rats underwent total subdiaphragmatic, bilateral selective celiac, or sham vagotomy. On day 28-32 after surgery, they were injected IP with Escherichia coli LPS (5, 20, or 100 microg/kg) or saline and decapitated 90 min thereafter. Their plasma levels of LPS and their plasma interleukin-6, adrenocorticotropin, and corticosterone responses to LPS were measured. Success of intraperitoneal administration of LPS was verified by increased interleukin-1beta and interleukin-6 concentrations in the peritoneal lavage fluid. Effectiveness of vagotomies was confirmed by increased stomach mass (food retention) and pancreas mass (hypertrophy). In the shams, LPS caused a dose-dependent endotoxemia and increased plasma levels of interleukin-6, adrenocorticotropin, and corticosterone. Neither celiac nor total vagotomy affected any of these responses. LPS escapes from the peritoneal cavity by two primary routes, viz., the hematogenous (via the portal vein) and lymphogenous (via the lymphatic system). The design of the present study did not allow for evaluating the rapid, hematogenous transport. The results obtained suggest that the abdominal vagus does not control the slow. lymphogenous escape of LPS from the peritoneal cavity.
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PMID:Lipopolysaccharide transport from the peritoneal cavity to the blood: is it controlled by the vagus nerve? 1118 20

Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are synthesized and released from adrenal cells. Therefore, the effects of TNF-alpha and IL-6 on cortisol release from bovine zona fasciculata (ZF) cells were investigated. IL-6 (10-1000 pg/mL) significantly increased basal and adrenocorticotropic hormone (ACTH)-stimulated cortisol release in a concentration-dependent manner. This stimulatory effect of IL-6 became apparent at intervals as short as 4 h and continued through 24 h. IL-6 also potentiated the cortisol release stimulated by the adenylyl cyclase activator forskolin. By contrast, TNF-alpha (0.1-10 ng) inhibited basal and ACTH-stimulated cortisol release in a concentration-dependent manner. The inhibitory effects of TNF-alpha on cortisol release were significant at time intervals as short as 4 h and continued through 24 h. TNF-alpha inhibited forskolin-stimulated cortisol release. Binding studies demonstrated that ZF cells have IL-6 receptors (100 receptors/cell, Kd of 7.5 x 10(-11)) and TNF receptors (200 receptors/cell, Kd of 2.4 x 10(-9) M). Immunohistochemical analysis provided evidence that the majority of ZF cells have IL-6 receptors, TNF type 1 receptors, and TNF type 2 receptors. Because IL-6 and TNF-alpha are released from the adrenal cortex and these cytokines modify the release of cortisol from the ZF, IL-6 and TNF-alpha may play a paracrine or autocrine role in the regulation of adrenal function.
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PMID:Stimulation by interleukin-6 and inhibition by tumor necrosis factor of cortisol release from bovine adrenal zona fasciculata cells through their receptors. 1121 50

The prevalence of chronic widespread pain in the general population in Israel was comparable with reports from the USA, UK, and Canada. Comorbidity with fibromyalgia (FM) resulted in somatic hyperalgesia in patients with irritable bowel syndrome. One sixth of the subjects with chronic widespread pain in the general population were also found to have a mental disorder. Mechanisms involved in referred pain, temporal summation, muscle hyperalgesia, and muscle pain at rest were attenuated by the N-methyl-D-aspartate (NMDA) antagonist, ketamine, in FM patients. Delayed corticotropin release, after interleukin-6 administration, in FM was shown to be consistent with a defect in hypothalamic corticotropin-releasing hormone neural function. The basal autonomic state of FM patients was characterized by increased sympathetic and decreased parasympathetic systems tones. The severity of functional impairment as assessed by the Medical Outcome Survey Short Form (SF-36) discriminated between patients with widespread pain alone and FM patients. Chronic fatigue syndrome (CFS) occurred in about 0.42% of a random community-based sample of 28,673 adults in Chicago, Illinois. A significant clinical overlap between CFS and FM was reported. Cytokine dysregulation was not found to be a singular or dominant factor in the pathogenesis of CFS. A favorable outcome of CFS in children was reported; two thirds recovered and resumed normal activities. No major therapeutic trials in FM and CFS were reported over the past year.
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PMID:Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome. 1122 36

The hypothalmus-pituitary-adrenal (HPA) axis and the immune system communicate at multiple levels: On the one hand, immune system-derived substances, such as interleukin-1, interleukin-6, tumor necrosis factor alpha, and leukemia inhibitory factor can stimulate the HPA axis. On the other hand, HPA axis-derived substances, most importantly glucocorticoids, can modulate the immune response. Furthermore, factors that were originally thought to be restricted to the HPA axis have been found to be expressed by immune cells. Proteins belonging to the CRH (corticotropin-releasing hormone) family represent important examples of such hormones. In the early 1990s, it was shown that immunoreactive CRH was present at sites of chemically induced inflammation. Administration of anti-CRH antibodies reduced the degree of inflammation, pointing to a pro-inflammatory role of "peripheral" CRH. We and others could show that lymphocytes are one source of immunoreactive CRH; however, the antiserum used in our study as well as in previous reports crossreacted with urocortin, a newly discovered member of the CRH family. Using RT-PCR, we could clearly demonstrate that human lymphocytes expressed urocortin but not CRH mRNA. These results were confirmed by immunocytochemistry, employing urocortin- and CRH-specific antibodies, respectively. The possible functional roles of urocortin expression in the immune system are discussed.
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PMID:The peripheral CRH/urocortin system. 1126 56

Anorexia nervosa (AN) patients have difficulty in establishing social contacts, leading to tension, anxiety and full-blown stress reactions. Stress hormones are chronically increased in AN, while immune function, which is involved in physical and psychological coping capacities, is mostly unimpaired. We examined immune function in a group of anorexics by measuring the T-lymphocyte proliferative response to stimulation with phytohemagglutinin (PHA), before and after in vivo acute administration of corticotropin-releasing hormone (CRH), to mirror a stress reaction. The responses of anorexics, before and after CRH stimulation, did not differ from those of controls. In a second group of anorexics, we measured plasma concentrations of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) before and after psychopharmacological (fluoxetine, amineptine) therapy. Basal values of the cytokines were not different in patients and controls, and did not change during therapy. In the same patients, we measured basal concentrations of soluble IL-1 beta receptor antagonist (s-IL-1 beta-RA), soluble IL-6 receptor (sIL-6-R) and soluble TNF-alpha receptors I and II (sTNF-alpha-R-I and -II). S-IL-1 beta-RA and sTNF-alpha-R-I and -II levels were not different in patients and controls, while those of s-IL-6-R were lower than normal in anorexics. The normality of most of the immune parameters in our anorexics, in basal conditions, after a stressful stimulation and after pharmacological manipulation of neurotransmitters suggests that the well-known interrelation among immune, neuroendocrine and central nervous system functions is not maintained in AN, the immune system being somehow unresponsive to stimuli.
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PMID:Social stress in anorexia nervosa: a review of immuno-endocrine relationships. 1143 63

Anorexia and weight loss are frequent complications of acute and chronic infections and result from induction of cytokines, prostaglandins, and other inflammatory mediators that are critical for pathogen elimination. Selective attenuation of the hypophagic response to infection and maintenance of the production of factors essential for infection control would be a useful addition to antimicrobial therapy in the treatment of human disease. Here, we evaluate the relative contribution of cyclooxygenase (COX)-1- and COX-2-derived prostaglandins to anorexia and weight loss precipitated by systemic immune activation by lipopolysaccharide (LPS). Using COX isoform-selective pharmacological inhibitors and gene knockout mice, we found that COX-2 inhibition during LPS-induced inflammation results in preserved food intake and maintenance of body weight, whereas COX-1 inhibition results in augmented and prolonged weight loss. Regulation of neuropeptide Y, corticotropin-releasing hormone, leptin, and interleukin-6 does not change as a function of COX-2 inhibition after LPS administration. Our data implicate COX-2 inhibition as a therapeutic target to maintain nutritional status while still allowing a normal cytokine response during infection.
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PMID:COX-2 inhibition attenuates anorexia during systemic inflammation without impairing cytokine production. 1183 69

Bi-directional communication between the hypothalamus-pituitary-adrenal (HPA)-axis and the sympathetic nervous system with the immune system is crucial to ensure homeostasis. Shared use of ligands and especially receptors forms a key component of this bi-directional interaction. Glucocorticoids (GC), the major end products of the HPA-axis differentially modulate immune function. Cytokines, especially interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), ensure immune signalling to the neuroendocrine system. In addition, hormones from leukocyte origin such as corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and beta-endorphin, as well as centrally synthesised and secreted cytokines, contribute to the communication network. In teleost fish cortisol is the major product of the hypothalamus-pituitary-interrenal (HPI)-axis which is the teleost equivalent of the HPA-axis. Moderate and substantial increases in cortisol during stressful circumstances negatively affect B-lymphocytes, whereas rescue of neutrophilic granulocytes may support innate immunity. Recent elucidation of lower vertebrate cytokine sequences has facilitated research into neuroendocrine-immune interactions in teleosts and the first evidence for a significant function of interleukin-1 in the bi-directional communication is discussed.
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PMID:Neuroendocrine-immune interactions in fish: a role for interleukin-1. 1207 74

Interleukin-6 (IL-6) is the end-product of a cytokine signaling cascade and is secreted by specialized immune cells during inflammation. It has a great influence on many functions, including differentiation, stimulation, and activation of immune cells, or other cells of neuroendocrine origin. Thus, IL-6 serves as a key messenger in its communication with the neuroendocrine system, and serves as a potent activator of the hypothalamic-pituitary-adrenal axis at all levels. Changes in the levels of expression of this cytokine and its receptor have been observed during chronic inflammatory disease, and have been associated with tumorigenesis. Therefore, we studied the effect of IL-6 on normal and adenomatous human adrenal cells in vitro. The expression of IL-6 receptor mRNA was quantified within the same tissue. IL-6 potently stimulated cortisol secretion from dispersed normal human adrenal cells. We found immunoreactivity for the IL-6 receptor on cultured cells and paraffin-embedded sections of adrenal tissues. Further, there was a more pronounced expression of IL-6 mRNA in adrenal adenomas of patients with Cushing's syndrome, compared to normal human adrenals. Despite this fact, the sensitivity of cells of adenomatous adrenal glands to IL-6 was significantly decreased relative to cells from normal controls. These results were confirmed employing the permanent adrenocortical cancer cell line model NCI-H295. We infer that the loss of responsivity of tumorous adrenal cells to IL-6, and in part corticotropin, is an important step in the process of adrenal tumorigenesis by which regulation by differentiating proteins is bypassed.
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PMID:Role of interleukin-6 in stress response in normal and tumorous adrenal cells and during chronic inflammation. 1211 87

Lewis (LEW/N) rats, compared to Fischer (F344/N) rats, are susceptible to inflammatory/autoimmune diseases, in part, as a result of their blunted hypothalamic-pituitary-adrenal (HPA) axis responses. We examined regulation of LEW/N and F344/N fetal hypothalamic cell secretion of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), two major HPA axis mediators, by inflammatory and neurotransmitter stimuli. Interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and protein kinase A (PKA) and protein kinase C (PKC) activators did not affect LEW/N basal secretion. Compared to F344/N, LEW/N cells were hyporesponsive to lipopolysaccharide (LPS), serotonin (5-HT), and acetylcholine chloride (ACh). However, LPS-induced AVP release and ACh-evoked CRH secretion in LEW/N were comparable with those of F344/N. Our findings suggest that the blunted LEW/N neuropeptide response was more likely related to components of second messenger systems, rather than to any one specific stimulus.
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PMID:Specific up-regulation of CRH or AVP secretion by acetylcholine or lipopolysaccharide in inflammatory susceptible Lewis rat fetal hypothalamic cells. 1245 34

Mesenteric ischemia-reperfusion injury is a serious complication of shock. Because activation of nuclear factor-kappaB (NF-kappaB) has been implicated in this process, we treated rats with vehicle or the IkappaB-alpha inhibitor BAY 11-7085 (25 mg/kg ip) 1 h before mesenteric ischemia-reperfusion (45 min of ischemia followed by reperfusion at 30 min or 6 h) and examined the ileal injury response. Vehicle-treated rats subjected to ischemia-reperfusion exhibited severe mucosal injury, increased myeloperoxidase (MPO) activity, increased expression of interleukin-6 and intercellular adhesion molecule 1 protein, and a biphasic peak of NF-kappaB DNA-binding activity during the 30-min and 6-h reperfusion courses. In contrast, BAY 11-7085-pretreated rats subjected to ischemia-reperfusion exhibited less histological injury and less interleukin-6 and intercellular adhesion molecule 1 protein expression at 30 min of reperfusion but more histological injury at 6 h of reperfusion than vehicle-treated rats subjected to ischemia-reperfusion. Studies with phosphorylation site-specific antibodies demonstrated that IkappaB-alpha phosphorylation at Ser(32),Ser(36) was induced at 30 min of reperfusion, whereas tyrosine phosphorylation of IkappaB-alpha was induced at 6 h of reperfusion. BAY 11-7085 inhibited the former, but not the latter, phosphorylation pathway, whereas alpha-melanocyte-stimulating hormone, which is effective in limiting late ischemia-reperfusion injury to the intestine, inhibited tyrosine phosphorylation of IkappaB-alpha. Thus NF-kappaB appears to play an important role in the generation and resolution of intestinal ischemia-reperfusion injury through different activation pathways.
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PMID:Effects of NF-kappa B inhibition on mesenteric ischemia-reperfusion injury. 1246 47


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