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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis, health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute-phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro- versus anti-inflammatory and T helper (Th)1 versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic 'overshooting' with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-alpha and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the 'systemic anti-inflammatory feedback' and/or 'hyperactivity' of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases.
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PMID:Cytokine dysregulation, inflammation and well-being. 1616 5

Metformin has been widely used in clinical type 2 diabetes treatment and prevention. The present study was designed to explore the effect on people with a sedentary lifestyle at therapeutic doses. Twenty-two physically-inactive volunteers with normal glucose tolerance were studied. Escalating doses of metformin in low-dose (250 mg), intermediate-dose (500 mg), and high-dose (750 mg) treatment three times per day were administrated into each subject for a three-week treatment period. Fasting plasma glucose, A1C, HOMA-IR for insulin resistance, lipid profile, and plasma beta-endorphin-like immunoreactivity (BER) were measured before treatment and weekly at the end of each dosing period. Metformin significantly reduced fasting plasma glucose and HOMA-IR in healthy humans after receiving this treatment at therapeutic doses including low-dose (5 %, 17 %), intermediate-dose (6 %, 25 %) and high-dose treatment (6 %, 21 %). Plasma BER was also increased from 135.46 +/- 61.73 pg/ml to 137.52 +/- 66.11 pg/ml by low-dosing (p = 0.39), to 139.17 +/- 64.08 pg/ml by intermediate-dosing (p = 0.32), and to 149.59 +/- 63.32 pg/ml by high-dosing (p < 0.05). Also, serum cholesterol decreased significantly using metformin at therapeutic doses including low-dose (4 %), intermediate-dose (8 %) and high-dose treatment (7 %). However, metformin failed to modify levels of serum HDL-cholesterol and C-reactive protein (CRP) in healthy subjects. Also, the reduction of serum cholesterol by metformin did not correlate to the increase in insulin sensitivity. In conclusion, metformin causes a significant parallel increase in insulin sensitivity and plasma beta-endorphin level in human subjects.
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PMID:Metformin increases insulin sensitivity and plasma beta-endorphin in human subjects. 1652 11

The information significance of the immunological indexes for the prognosis of gravity of course and of outcome of an acute radiation disease for the people after the exposure of ionizing radiation in clinically significant doses is studied. The value of indexes of the C-reactive protein contents, of the complement contents and of the titer of haemagglutinins in serum of a blood of 147 patients damaged at Chernobyl NPP accident as a result of external radiation gamma-exposure in combination with internal irradiation from the incorporation in an organism predominantly beta-emitting radionuclides were compared to the weight of acute radiation disease and its outcome (survival or loss). Was determined, that indexes of the contents of C-reactive protein in a peripheral blood during primary reactions on the irradiation (1-2 day after irradiation) and in latent period of disease (3-9 day after irradiation), and also titer of a complement on 3-9 day after irradiation can serve a source of information for the prognosis of probable gravity of a radiation injury and its outcome at irradiation of the man in clinically significant doses.
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PMID:[The individual prognosis of the gravity and of the outcome of acute radiation disease based on immunological indexes]. 1675 12

The hypothalamic-pituitary-adrenal axis is an essential component for the maintenance of homeostasis following trauma. Major surgical trauma often induces overwhelming inflammatory responses leading to sepsis and organ dysfunction. This study was designed to evaluate the adrenal responses both before and after various degrees of surgical trauma and to determine the incidence of postoperative relative adrenal insufficiency resulting in the marked inflammatory response often associated with postoperative complications. Fifty-one surgical patients were divided into groups who underwent major, moderate, and minor surgeries. Before the operation and during resting conditions, a short corticotropin (ACTH) stimulation test was performed in each patient. The postoperative concentrations of serum cortisol, interleukin (IL)-6, IL-10, C-reactive protein (CRP), and plasma ACTH were measured. Fifty of 51 patients were identified as responders to ACTH. The postoperative cortisol levels were the same as those obtained by ACTH stimulation in highly and moderately stressful surgeries. The increases in postoperative IL-6 and CRP levels were greatest with major surgery, intermediate with moderate surgery, and least with minor surgery. Furthermore, plasma ACTH levels increased after major and moderate surgeries; however, there was no significant differences in postoperative serum IL-10 levels. Systemic inflammatory response syndrome (SIRS) was found in 11 of 17 patients (64.7%) who underwent major surgery and in 4 of 16 patients (25%) who underwent moderate surgery (p=0.037). The duration of SIRS was significantly longer in patients undergoing major surgery (62+/-20 hrs) than in patients undergoing moderate surgery (21+/-3 hrs, p=0.038). Postoperative complications were more frequent in patients undergoing major surgery (41.2%) than in patients undergoing moderate surgery (6.3%, p=0.039). Furthermore, there were significant differences in the length of the postoperative stay among the three groups (p<0.01). One nonresponder had serious postoperative inflammatory complications. These results suggest that a short ACTH stimulation test performed preoperatively is a helpful method for determining the maximal cortisol response to surgical trauma and to identify high-risk individuals and that a relative postoperative adrenal insufficiency may be closely related to the decreased cortisol secretion following major surgical trauma.
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PMID:Surgical trauma-induced adrenal insufficiency is associated with postoperative inflammatory responses. 1787 97

1. Differences in blood lipids, glucose, insulin, amylin, adrenocorticotropic hormone (ACTH), cortisol, aldosterone, angiotensin II, metabolites of nitric oxide (nitrate, nitrite), asymmetric dimethyl arginine, endothelial leucocyte adhesion molecule-1, vascular cell adhesion molecule-1, C-reactive protein, homocysteine and oxidative status (urate, vitamin A, vitamin E, beta-carotene and total anti-oxidant capacity) were investigated in men (aged 18-25 years) with (+) or without (-) a family history (FH) of hypertension. 2. In the present study, FH+ was defined as having at least one parent or grandparent taking medication for hypertension. Blood (60 mL) was sampled (0800-1000 hours) from a cannulated forearm vein after an overnight fast and 24 h abstinence from caffeine-containing products and alcohol. 3. Comparing FH+ with FH-, systolic blood pressure (124 +/- 1 vs 117 + 3 mmHg, respectively; n = 50 and 14, respectively; P < 0.05) and plasma cortisol (377 +/- 23 vs 298 +/- 24 nmol/L, respectively; n = 43 and 12, respectively; P < 0.05) were found to be significantly higher in the former group. 4. No significant difference was found between the two groups for body mass index, resting heart rate, diastolic and mean blood pressures or any of the biochemical measures studied. 5. A significant correlation was found between cortisol and ACTH (r = 0.73). No correlation was found between cortisol and any other parameter measured. 6. These data indicate that elevated cortisol levels are characteristic of young lean normotensive FH+ men. The future impact of this on their vascular health and hypertension remains to be determined.
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PMID:Elevated levels of circulating cortisol in young normotensive adult men with a family history of hypertension. 1806 96

Allostatic load (AL) is a theoretical framework that describes the cumulative physiologic effects of adaptation to change or stress throughout the lifespan. AL is operationalized by a composite index of multiple biomarkers. Accordingly, genes, behavior and environment contribute to AL. To determine if individual differences in AL may be influenced by inherent genetic variation, we calculated an allostatic load index (ALI) for 182 Caucasian subjects derived from a population-based study of chronic fatigue syndrome. Nearly 65% of the subjects in this study sample reported fatiguing illness. ALI was calculated based on 11 measures representing metabolic, cardiovascular, inflammatory, hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) activities. Subjects were dichotomized into high (ALI > or = 3) or low (ALI < 3) AL groups, and the association between high AL and 129 polymorphisms in 32 genes related to the HPA axis, neurotransmission, inflammation, cardiovascular and metabolic functions were evaluated. Polymorphisms in angiotensin-1 converting enzyme (ACE), corticotropin-releasing hormone receptor 1 (CRHR1), and serotonin receptors (HTR3A and HTR4) were associated with AL (p=0.0007-0.0486), but only one polymorphism, rs4968591, in ACE remained significant after correction for multiple comparisons. The T allele of ACE rs4968591 was more common in subjects with high AL (67.5%) than in subjects with low AL (49.3%) (p=0.0007), and this effect appeared independent of age, sex, body mass index and fatigue status. Additionally, high interleukin-6 (IL-6; p(trend)=0.04), and C-reactive protein (CRP; p(trend)=0.01) levels, as well as low urinary cortisol levels in females (p=0.03) were associated with the T allele, which may result in allele-specific binding of the transcription factor, E2F1. Our results suggest a role for ACE in the bidirectional communication between the central nervous and immune systems in response to stress. Further studies will be needed (a) to replicate the association between AL and ACE polymorphisms in population studies designed to differentiate the effects of sex, age and racial/ethnic background, (b) to evaluate the effect of allele-specific binding of E2F1 at rs4968591, and (c) to examine the role of ACE in the co-regulation of CRP, IL-6 and cortisol.
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PMID:An angiotensin-1 converting enzyme polymorphism is associated with allostatic load mediated by C-reactive protein, interleukin-6 and cortisol. 1908 78

The aim of our study was to evaluate the neuroendocrine system in patients with juvenile idiopathic arthritis (JIA) regarding the activity of disease. Twenty-one JIA patients (mean age +/- standard deviation 10.5 +/- 4.1 years) were included. None of the patients was taking steroids or antitumor necrosis factor-alpha therapy during this study. Ten healthy volunteers and ten volunteers with upper respiratory tract infection composed the control groups. Furthermore, ten of the 21 JIA patients were also evaluated during the remission period. Erythrocyte sedimentation rate, C-reactive protein, adrenocorticotropic hormone (ACTH), cortisol, prolactin, insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein 3, free T3, free T4, thyroid-stimulating hormone, interleukin-6 (IL-6) levels, and 24-h urinary cortisol were evaluated both during the active period and remission. The median levels of ACTH and cortisol at 08:00 a.m. were significantly lower in patients with active JIA than patients in remission period and the control groups (p < 0.05). Furthermore, the median level of urine cortisol in active JIA patients was significantly lower than remission period and control groups (p < 0.05). The median level of IGF-1 was significantly lower in active patients than that of remission (p < 0.05). The median level of IL-6 in active JIA patients was significantly higher than those in remission and control groups (p < 0.05). Our preliminary study suggested that impaired secretion of adenohypophyseal hormones and distorted bilateral interactions between the immune and endocrine systems in JIA. Further studies are needed to clarify the consequences of the impaired hormone secretion in JIA.
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PMID:Low cortisol levels in active juvenile idiopathic arthritis. 2001 15

Familial Mediterranean fever (FMF) is an autoinflammatory disorder and is characterized by self-limited attacks of inflammation. Although mutations in the gene coding for pyrin are responsible for the inflammation seen in attacks, the question of whether the failure to mount an appropriate cortisol response to inflammation has any additive effects allowed us to plan this study. The aim was to determine the interactions between the neuroendocrine and immune system in patients with FMF and investigate the role of the neuroendocrine system in the acute inflammation process. Demographic characteristics, disease activity, mutation analysis, and duration of the disease were defined in 15 FMF patients (7 female, 8 male; mean age +/- SD: 9.1 +/- 4.2 years). The diagnosis was based on Tel-Hashomer criteria. Ten healthy volunteers and 21 active juvenile idiopathic arthritis (JIA) patients formed the control groups. Furthermore, 10 of these 15 patients with FMF were also studied during the attack-free period. Erythrocyte sedimentation rate (ESR) C-reactive protein (CRP), fibrinogen, adrenocorticotropic hormone (ACTH), cortisol, insulin-like growth factor-1 (IGF)-1, IGF binding protein (BP)-3, urinary cortisol levels, interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-a were evaluated in FMF patients with attack and during the attack-free period. Although the median levels of ACTH (12.7 pg/ml) and cortisol (12 ug/dl) at 08:00 a.m. were lower in FMF patients during attack than in the attack-free period, these differences did not reach statistical significance. On the other hand, the median levels of ACTH were significantly lower during attack than in the healthy control group (p < 0.05). Median levels of IGF-1 (118.5 ng/ml) were significantly lower during FMF attack than in the attack-free period (p < 0.05). There was a negative correlation between IGF-1 and CRP (r = -0.47). The median level of IL-6 was 18.1 pg/dl during FMF attack and was significantly higher than in the attack-free period and in the healthy control group (p < 0.05). There was a negative correlation between cortisol level at 08:00 am and IL-6 (r = -0.45). When we compared JIA with FMF patients during attack, inappropriately low secretion of adrenal cortisol and ACTH and low urine cortisol levels were more pronounced in JIA than FMF Although it is more prominent in chronic inflammation, the neuroendocrine immune system seems to be impaired in relation to acute inflammation in FMF.
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PMID:Neuroendocrine immune system in familial Mediterranean fever. 2142 90

It is still unclear whether the association between traumatic stress and physical disease is mediated by posttraumatic stress disorder (PTSD). Therefore, we examined the long-term consequences of PTSD on cardiovascular risk, stress hormones, and quality of life in a sample of former refugee children who were severely traumatized more than six decades ago. In 25 subjects with chronic PTSD and 25 trauma-controlled subjects, we measured the variables of metabolic syndrome supplemented by the ankle-brachial index and highly sensitive C-reactive protein. Quality of life was assessed using the 36-item Short-Form Health Survey. Cortisol, adrenocorticotropin-releasing hormone (ACTH), and dehydroepiandrosterone (DHEA) were measured using the low-dose-dexamethasone suppression test. In addition, salivary cortisol was assessed at 8:00 a.m., 12:00 p.m., 4:00 p.m., and 8:00 p.m. We found a significant group effect between participants with and without PTSD regarding quality of life but not in any metabolic parameter including the ankle-brachial index or cortisol, ACTH, and DHEA in plasma before and after dexamethasone or salivary cortisol. The postulated association between traumatic stress and physical illness does not appear to be mediated by PTSD in this population. Nevertheless, the search for subgroups of PTSD patients with childhood traumatization leading to different metabolic and endocrine long-term consequences in aging PTSD patients is needed.
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PMID:Effects of chronic posttraumatic stress disorder on metabolic risk, quality of life, and stress hormones in aging former refugee children. 2187 77

Large numbers of polymorphonuclear leukocytes in the amnion and chorion define histological chorioamnionitis (HCA), a condition linked to spontaneous preterm delivery (PTD). Less is known about placental patterns of mononuclear leukocyte (MNL) density and PTD. In this prospective study (1998-2004), women were sampled from 52 clinics in 5 Michigan communities and enrolled at 16-27 weeks' gestation. HCA and MNL distributions in delivered placentas were evaluated microscopically in a subcohort (290 preterm, 823 term). Midpregnancy biomarkers from maternal blood (i.e., C-reactive protein (CRP), corticotropin-releasing hormone, and cytokines) were compared among term and PTD subjects grouped by presence/absence of HCA and high MNL density. A density of more than 10 MNLs per high-power field in the chorion of the membrane roll, referred to as MNL-CMR, was associated with medically indicated PTD (odds ratio = 2.2, 95% confidence interval: 1.3, 3.6) and spontaneous PTD (odds ratio = 2.5, 95% confidence interval: 1.7, 3.7). Associations persisted after removal of women with HCA-positive placentas, abruption, hypertensive disorders, or obesity. HCA-associated PTD showed higher CRP and cytokine levels. MNL-CMR-associated PTD showed higher CRP and corticotropin-releasing hormone levels. These data suggest that an MNL infiltrate in the chorion of the membrane roll marks PTD pathways that are distinct from HCA and not entirely explained by pregnancy complications.
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PMID:Mononuclear leukocyte infiltrate in extraplacental membranes and preterm delivery. 2342 23


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