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)

Stress is known to either up or down regulate immunity. In this study, mice were subjected to handling combined with rectal temperature measurement (RTM) stress or handling only stress. We investigated whether there were any significant differences in the effect of handling combined with RTM and handling only on NK cell activity, serum cytokine (IL-1beta, IL-6, and TNF-alpha) and ACTH and beta-endorphin levels, and splenic cytokine (IL-1beta, IL-6, TNF-alpha, IFN-alpha, and IFN-beta) levels. Circulating cytokines and hormones and splenic cytokine mRNA levels were measured in individual mice. NK cell activity was significantly increased in both stress groups when compared to the control group. Handling combined with RTM produced significantly increased serum levels of IL-1beta, IL-6, and beta-endorphin. Serum IL-1beta, ACTH, and beta-endorphin were elevated significantly in the handling only group. Splenic TNFalpha mRNA in both of the stress groups and IL-6 mRNA in handling only group decreased significantly. Our observations are supported by existing literature demonstrating that various stressors have differential effects on immune functions and the neuroendocrine hormones and cytokines, which regulate them.
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PMID:Cytokine and hormone profiles in mice subjected to handling combined with rectal temperature measurement stress and handling only stress. 1253 17

There is a substantial body of evidence that the tridecapeptide alpha-melanocyte-stimulating hormone (alpha-MSH) functions as a mediator of immunity and inflammation. The immunomodulating capacity of alpha-MSH is primarily because of its effects on melanocortin receptor (MC-1R)-expressing monocytes, macrophages, and dendritic cells (DCs). alpha-MSH down-regulates the production of proinflammatory and immunomodulating cytokines (IL-1, IL-6, TNF-alpha, IL-2, IFN-gamma, IL-4, IL-13) as well as the expression of costimulatory molecules (CD86, CD40, ICAM-1) on antigen-presenting DCs. In contrast, the production of the cytokine synthesis inhibitor IL-10 is up-regulated by alpha-MSH. At the molecular level, these effects of alpha-MSH are mediated via the inhibition of the activation of transcription factors such as NFkappaB. Not only alpha-MSH but also its C-terminal tripeptide (alpha-MSH 11-13, KPV) was able to bind to MC-1R and to modulate the function of APCs. In vivo, using a mouse model of contact hypersensitivity (CHS) systemic and topical application of alpha-MSH or KPV inhibited the sensitization and the elicitation phase of CHS and was able to induce hapten-specific tolerance. To investigate the underlying mechanisms of tolerance induction, we have performed in vivo transfer experiments. Treatment of naive mice with bone marrow-derived immature haptenized and alpha-MSH-pulsed DCs resulted in a significant inhibition of CHS. Furthermore, tolerance induction was found to be mediated by the generation of CTLA4(+) and IL-10-producing T lymphocytes. The potent capacity of alpha-MSH to modulate the function of antigen-presenting cells (APCs) has been further supported in another experimental approach. In vitro, by activating APCs, alpha-MSH has been shown to modulate IgE production by IL-4 and anti-CD40 stimulated B lymphocytes. Moreover, in a murine model of allergic airway inflammation, systemic treatment with alpha-MSH resulted in a significant reduction of allergen-specific IgE production, eosinophil influx, and IL-4 production. These effects were mediated via IL-10 production, because IL-10 knockout mice were resistant to alpha-MSH treatment. Therefore, therapeutic application of alpha-MSH or related peptides (KPVs) as well as alpha-MSH/KPV-pulsed DCs may be a useful approach for the treatment of inflammatory, autoimmune, and allergic diseases in the future.
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PMID:New insights into the functions of alpha-MSH and related peptides in the immune system. 1285 8

Polymorphonuclear leukocyte (neutrophil) apoptosis is an important mechanism regulating the life span and some functions of neutrophils at inflamed sites. Opioid peptides are present in the peripheral circulation and their concentrations rapidly increase as a result of stress and inflammation. The effect of opioid peptides such as met-enkephalin (M-ENK) and beta-endorphin (beta-END) on tumor necrosis factor (TNF)-alpha-induced apoptosis in human neutrophils in vitro was investigated. Neutrophils isolated from peripheral blood were cultured in the absence or presence of 10(-6)-10(-10) M of opioid peptides for 8, 12 and 18 h. Features of apoptotic neutrophils were measured by a flow cytometric method based on analysis of the apoptotic nuclei (DNA content). We found that M-ENK and beta-END enhanced both uninduced and TNF-alpha-induced neutrophil apoptosis in vitro in a dose-dependent manner. The effect of opioid peptides on the modulation of neutrophil apoptosis was not reversed by the opioid-receptor antagonist naloxone. The results suggest that M-ENK and beta-END can regulate neutrophil life span via apoptosis and in this way may participate in the resolution of inflammation.
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PMID:Effect of exogenous opioid peptides on TNF-alpha-induced human neutrophil apoptosis in vitro. 1295 36

Dysfunction of the hyopthalamo-pituitary adrenal (HPA) system is frequently found in major depression. In addition, signs of non-specific inflammatory system activation have been reported. However, very little is known about interactions between the HPA and immune systems in depressive patients. To assess HPA system function, we performed a combined dexamethasone suppression and corticotropin-releasing hormone stimulation (DEX/CRH) test in 14 depressive patients. Moreover, baseline nocturnal plasma levels of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were measured. In addition, the system was challenged with an intraveneous pulsatile injection of hydrocortisone (1 mg/kg body weight in total) and again cytokine levels were measured across one night. Baseline TNF-alpha levels were negatively correlated with the amount of ACTH released upon CRH stimulation during the DEX/CRH test. Acute hydrocortisone administration suppressed TNF-alpha and IL-6 levels independently of baseline HPA system activity. We conclude that chronic HPA system overactivity in depressed patients might compromise the production of inflammatory cytokines under baseline conditions. However, the responsivity of the cytokine production to acutely administered glucocorticoids does not seem to correlate with the state of the HPA system.
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PMID:Hypothalamo-pituitary-adrenal function in patients with depressive disorders is correlated with baseline cytokine levels, but not with cytokine responses to hydrocortisone. 1456 77

Since the earliest descriptions psychological and physical stress has been considered a controversial but potentially important factor in the onset and course of multiple sclerosis (MS). During recent years it has become clear that MS patients benefit from physical exercise as performed in aerobic training. As acute exercise has profound effects on immune and endocrine parameters we studied endocrine and immune response to standardized physical stress in MS within a study of aerobic training. Fifteen MS patients completed an eight-week aerobic training program, 13 patients were part of a wait-control group. Twenty healthy controls were recruited as well. A step-by-step bicycle ergometry was performed to determine individual exertion levels. For the endurance test patients exercised at 60% VO2 max for 30 min. Blood samples were drawn before, directly after and 30 min after completion of the exercise. Heart rate and lactate increased in all groups (p<.0001). We furthermore saw significant increases in endocrine parameters (epinephrine, norepinephrine, ACTH, and beta-endorphin; all p<.0001) in healthy individuals and in MS patients but without a differential effect. Whole-blood stimulated production of IFN-gamma (IFNgamma) was induced similarly in all groups (p<.01). TNF-alpha (TNFalpha) and IL-10 were less inducible in MS patients (trend). From these data we could not demonstrate a proinflammatory immune deviation in response to physical stress in MS. The observed trend of hyporesponsive TNFalpha and IL-10 responses in MS warrants further investigation.
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PMID:Endocrine and cytokine responses to standardized physical stress in multiple sclerosis. 1458 39

Ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor and some GHSs exert different effects on sleep electroencephalogram (EEG) and sleep-related hormone secretion in humans. Similar to GH-releasing hormone (GHRH) ghrelin promotes slow-wave sleep in humans, whereas GH-releasing peptide-6 (GHRP-6) enhances stage 2 nonrapid-eye movement sleep (NREMS). As GHRP-6, hexarelin is a synthetic GHS. Hexarelin is superior to GHRH and GHRP-6 in stimulating GH release. The influence of hexarelin on sleep-endocrine activity and the immune system is unknown. We investigated simultaneously the sleep EEG and nocturnal profiles of GH, ACTH, cortisol, prolactin, leptin, tumor necrosis factor (TNF)-alpha, and soluble TNF-alpha receptors in seven young normal volunteers after repetitive administration of 4 x 50 microg hexarelin or placebo at 22.00, 23.00, 24.00 and 01.00 h. Following hexarelin, stage 4 sleep during the first half of the night, and EEG delta power during the total night decreased significantly. Significant increases of the concentrations of GH and prolactin during the total night, and of ACTH and of cortisol during the first half of the night were found. Leptin levels, TNF-alpha and soluble TNF receptors remained unchanged. We hypothesize that sleep is impaired after hexarelin since the GHRH/corticotropin-releasing hormone (CRH) ratio is changed in favour of CRH. There are no hints for an interaction of hexarelin and the immune system.
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PMID:Hexarelin decreases slow-wave sleep and stimulates the secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers. 1517

Resistin is an adipocyte-secreted hormone proposed to link obesity with insulin resistance and diabetes, but no previous study has performed a joint quantitative evaluation of white adipose tissue (WAT) resistin mRNA expression and serum levels in relation to insulinemia and glycemia in mice. We have thus comparatively assessed WAT resistin mRNA expression and serum resistin levels in lean C57BL/6J mice and various mouse models of obesity, including diet-induced obese (DIO) C57BL/6J mice, high fat-fed TNF-alpha-/- mice, and brown adipose tissue (BAT)-deficient uncoupling protein-diphtheria toxin A chain (UCP1-DTA) mice. We also studied whether treatment with the weight-reducing and insulin-sensitizing compounds, MTII, an alpha-melanocyte-stimulating hormone analog, or CNTF(Ax15), a ciliary neurotrophic factor analog, alters resistin mRNA expression and/or circulating levels in lean and DIO C57BL/6J mice. We find that resistin mRNA expression is similar in DIO and lean C57BL/6J mice, as well as in TNF-alpha-/- and wild-type (WT) mice. Circulating resistin levels, however, are higher in DIO C57BL/6J, high fat-fed TNF-alpha-/-, and UCP1-DTA mice compared with lean controls. Moreover, although resistin mRNA expression is upregulated by MTII treatment for 24 h and downregulated by CNTF(Ax15) treatment for 3 or 7 days, circulating resistin levels are not altered by MTII or CNTF(Ax15) treatment. In addition, serum resistin levels, but not resistin mRNA expression levels, are correlated with body weight, and neither resistin mRNA expression nor serum resistin levels are correlated with serum insulin or glucose levels. We conclude that transcriptional regulation of resistin in WAT does not correlate with circulating resistin levels and that circulating resistin is unlikely to play a major endocrine role in insulin resistance or glycemia in mice.
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PMID:Circulating resistin in lean, obese, and insulin-resistant mouse models: lack of association with insulinemia and glycemia. 1552 96

Factors which induce the corpus luteum persistent (CLP) creation in animal ovaries are located in the hypothalamic-pituitary-ovarian axis and also in the uterus. In cows and likewise in others animals, various mediators of inflammatory reaction are released, mainly proinflammatory cytokines from inflamed uterus into the blood and lymph. Afterwards the cytokines cross the blood-brain barrier, and though the brain mediators alter the hormonal profile and amplitude pulses of the hormones release in the hypothalamus and the pituitary. Until it is known, that cytokines: IL-1, IL-2, IL-6, TNF-alpha and also IFN-alpha, administered into the median eminence, cause an increase in corticotrophin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) concentrations and decrease in the pituitary gland hormones secretion. The immune system, represented in the corpora lutea (CL) by numerous macrophages/monocytes, limphocytes and neutrophils plays an important role in the luteolysis process. The stimulating factor of the infiltration of these cells is an increased PRL level. The preovulatory increase in PRL level regulates the number of macrophages in newly-formed CL and later influences the number of these cells in the luteolysis period. The pulsatory release and high levels of the hypophyseal oxytocin (OT) and uterine PGF2alpha ensure the beginning and the normal course of the luteolysis period. The cytokines decrease OT concentration and disorder its pulsatory release from the pituitary. In these circumstances the quantity of the uterine PGF2alpha reaching ovaries, is insufficient to begin luteolysis. In the inflamed uterus, the elevation of PGE2 and PGI2 synthesis takes place. Both prostaglandins cause smooth uterine muscles relaxation and the dilatation of blood and lymph vessels in this organ. In these conditions, the blood and lymph outflow from the uterus is several times slower than in the control animals. The secretion of P4 and E2 from CLP, in comparison with control animals, is significantly lower. Decreased P4 concentration during the luteal phase of the estrous cycle, and E2 in the initiation of the luteolysis period, may cause the insufficient preparation of the endometrium for hypophyseal OT activity. Finally, we can assume that the creation of the CLP in the animal ovary is an exceptionally complex and not yet fully understood process.
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PMID:Immuno-endocrine mechanisms connected with the creation of corpora lutea persistent in animal ovaries. 1618 May 88

alpha-MSH has potent antiinflammatory properties, but little is known about the specific melanocortin receptors (MC-Rs) that mediate these effects or about the role of the melanocortin system in modulating cytokine responses to an inflammatory challenge in the primate in vivo. We, therefore, studied the effects of infusion of the alpha-MSH agonist, [Nle(4),d-Phe(7)]-alpha-MSH (NDP-MSH); the alpha-MSH antagonist, SHU9119; and the selective MC3-R agonist, D-Trp8-gamma-MSH, compared with saline, on proinflammatory cytokine (TNF-alpha, IL-1beta, and IL-6), antiinflammatory cytokine [IL-10 and IL-1 receptor antagonist (IL-1ra)], and pituitary-adrenal responses to endotoxin in ovariectomized monkeys. In the first study NDP-MSH or SHU9119 was infused iv for 7 h starting at 0800 h, endotoxin was injected at 1000 h, and serial blood samples were collected (n = 6). NDP-MSH significantly attenuated proinflammatory cytokine responses to endotoxin. The area under the response curve (AUC) decreased by 61% for TNF-alpha (P = 0.02), 47% for IL-1beta (P = 0.02), and 41% for IL-6 (P = 0.04); there was no effect on IL-1ra or IL-10. SHU9119 did not affect proinflammatory cytokine responses, but decreased the IL-10 response by 31% (P = 0.03). NDP-MSH also attenuated ACTH (P < 0.001) and cortisol (P = 0.02) responses. In a second study, the effects of d-Trp8-gamma-MSH were similarly examined in seven monkeys. The AUC for IL-6 was decreased by 37% (P = 0.04) by d-Trp8-gamma-MSH; the AUC for IL-10 was increased by 22%, but this was not significant. However, the ratio of IL-6 to IL-10 was significantly decreased by d-Trp8-gamma-MSH (P = 0.04), consistent with a relatively more antiinflammatory cytokine environment. These results indicate that NDP-MSH can attenuate proinflammatory cytokine responses in the primate, consistent with previous studies in the rodent, and provide new evidence for a role for MC3-R in this process. Moreover, they show for the first time that SHU9119, a mixed MC3/4-R antagonist, can decrease the IL-10 response, establishing a physiological role for endogenous MSH in modulating the release of an antiinflammatory cytokine.
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PMID:Melanocortin modulation of inflammatory cytokine and neuroendocrine responses to endotoxin in the monkey. 1641 Feb 97

Associations between stress and health outcomes have now been carefully documented, but the mechanisms by which stress specifically influences disease susceptibility and outcome remain poorly understood. Recent evidence indicates that glucocorticoids (GCs) and catecholamines (CAs), the major stress hormones, inhibit systemically IL-12, TNF-alpha, and INF-gamma, but upregulate IL-10, IL-4, and TGF-beta production. Thus, during an immune and inflammatory response, the activation of the stress system, through induction of a Th2 shift may protect the organism from systemic "overshooting" with T helper lymphocyte 1 (Th1)/proinflammatory cytokines. In certain local responses and under certain conditions, however, stress hormones may actually facilitate inflammation, through induction of IL-1, IL-6, IL-8, IL-18, TNF-alpha, and CRP production, and through activation of the corticotropin-releasing hormone (CRH)/substance P(SP)-histamine axis. Autoimmunity, chronic infections, major depression, and atherosclerosis are characterized by a dysregulation of the pro/anti-inflammatory and Th1/Th2 cytokine balance. Thus, hyperactive or hypoactive stress system, and a dysfunctional neuroendocrine-immune interface associated with abnormalities of the "systemic anti-inflammatory feedback" and/or "hyperactivity" of the local proinflammatory factors may contribute to the pathogenesis of these diseases. Conditions that are associated with significant changes in stress system activity, such as acute or chronic stress, cessation of chronic stress, pregnancy and the postpartum period, or rheumatoid arthritis (RA) through modulation of the systemic or local pro/anti-inflammatory and Th1/Th2 cytokine balance, may suppress or potentiate disease activity and/or progression. Thus, stress hormones-induced inhibition or upregulation of innate and Th cytokine production may represent an important mechanism by which stress affects disease susceptibility, activity, and outcome of various immune-related diseases.
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PMID:Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases. 1685 35


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