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)

It is known that the pituitary-adrenal responses to lipopolysaccharide and interleukin (IL)-1 are sexually dimorphic in rodents, with females having an enhanced secretion of adrenocorticotropin (ACTH) and corticosterone. This study investigated whether the ACTH and corticosterone responses to tumor necrosis factor (TNF)-alpha and IL-6, two principal proinflammatory cytokines, are also modulated by the sex steroid milieu in the rat. Mature male and female rats received an intravenous administration of TNF-alpha(10 microg/kg) and IL-6 (10 microg/kg), and changes in plasma ACTH and corticosterone levels were determined over time. The effect of gonadectomy on the hormonal responses was also examined in both sexes. TNF-alpha induced significantly higher responses of ACTH and corticosterone in females than in males, and this sexual difference was abolished by gonadectomy in both sexes. By contrast, the hormonal responses to IL-6 were not significantly affected by either gender or gonadectomy. These results suggest a sex steroid-dependent modulation of the TNF-alpha-induced, but not the IL-6-induced, ACTH and corticosterone secretion in the rat. Further evidence for the sexually dimorphic neuroimmunoendocrine activity is reported herein.
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PMID:Sexual dimorphism in the pituitary-adrenal response to tumor necrosis factor-alpha, but not to interleukin-6, in the rat. 1184 20

Nuclear factor-kappaB (NF-kappaB) and glucocorticoid receptor-alpha (GR-alpha) have diametrically opposed functions in regulating inflammation. We investigated whether unresolving acute respiratory distress syndrome (ARDS) is associated with systemic inflammation- induced glucocorticoid resistance and whether prolonged methylprednisolone administration accelerates the suppression of systemic inflammatory indices and normalizes the sensitivity of the immune system to glucocorticoids. Patients enrolled into a randomized trial evaluating prolonged methylprednisolone administration in unresolving ARDS had serial plasma samples collected before and after randomization. In the plasma, we measured the concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukins (IL) IL-1beta and IL-6, adrenocorticotropic hormone (ACTH), and cortisol. The ability of patient plasma to influence the NF-kappaB and GR-signal transduction systems of normal peripheral blood leukocytes (PBL) was examined. Patients treated with methylprednisolone had progressive and sustained reductions of TNF-alpha, IL-1beta, IL-6, ACTH, and cortisol concentrations over time. Normal PBL exposed to plasma samples collected during methylprednisolone exhibited significant progressive increases in all aspects of GR-mediated activity and significant reductions in NF-kappaB DNA-binding and transcription of TNF-alpha and IL-1beta. These findings provide support for the presence of endogenous glucocorticoid inadequacy in the control of inflammation and systemic inflammation-induced peripheral glucocorticoid resistance in ARDS. Prolonged methylprednisolone administration accelerated the resolution of both systemic inflammation and peripheral acquired glucocorticoid resistance in ARDS.
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PMID:Prolonged methylprednisolone treatment suppresses systemic inflammation in patients with unresolving acute respiratory distress syndrome: evidence for inadequate endogenous glucocorticoid secretion and inflammation-induced immune cell resistance to glucocorticoids. 1193 26

Infection with pathogens often leads to loss of body weight, but the cause of weight loss during infection is poorly understood. We used the infection of mice with lymphocytic choriomeningitis virus (LCMV) as a model to study how pathogens induce weight loss. If LCMV is introduced into the CNS of CTL-deficient mice, the immune response against the virus leads to a severe weight loss called wasting disease. We planned to determine what components of this antiviral immune response mediate wasting disease. By adoptive transfer, we show that CD4 T cells activated by LCMV infection are sufficient to cause wasting disease. We examined the role of cytokines in LCMV-induced wasting disease using mice lacking specific cytokines or cytokine receptors. Results of adoptive transfer experiments suggest that TNF-alpha is not involved in LCMV-induced wasting disease and show that IFN-gamma contributes to the disease. Consistent with a role for IFN-gamma in wasting, we find that IFN-gamma is necessary for LCMV-specific CD4 T cell responses in the CNS, most likely because it is required to induce MHC class II expression. Our data also indicate that IL-1 is required for LCMV-induced wasting and that IL-6 contributes to the wasting disease. Additionally, our results identify alpha-melanocyte-stimulating hormone as a potential mediator of the disease. Overall, this work defines the critical role of virus-primed CD4 T cells and of proinflammatory cytokines in the pathogenesis of wasting disease induced by LCMV infection.
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PMID:The role of proinflammatory cytokines in wasting disease during lymphocytic choriomeningitis virus infection. 1207 63

We used beta-endorphin-deficient mice as a novel approach to confirm the physiological role that opioid peptides play in the development or regulation of the immune system. We found that mice lacking beta-endorphin possessed an enhanced immune response, measured in terms of splenocyte proliferation and interleukin (IL)-2 mRNA levels, in vitro production of the splenic macrophage inflammatory cytokines IL-6 and Tumor Necrosis Factor (TNF)-alpha and plasma IL-6 following lipopolysaccharide (LPS) administration. beta-Endorphin-deficient mice had attenuated increases of plasma ACTH and corticosterone levels in response to LPS. These results are consistent with a postulated inhibitory role of endogenous beta-endorphin on the immune system at multiple levels.
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PMID:Increased splenocyte proliferative response and cytokine production in beta-endorphin-deficient mice. 1245 44

We investigated the effect of immune challenge with LPS in both control rats and rats with adjuvant-induced arthritis (AA). Fourteen day-AA rats showed the expected activation of the hypothalamic-pituitary adrenal axis associated with increases in vasopressin mRNA and paradoxical decreases in corticotropin-releasing hormone (CRH) mRNA in parvocellular neurons of the hypothalamic paraventricular nucleus (PVN). However, following LPS there was an increase in both CRH and vasopressin mRNA in the PVN. Neither control rats nor rats with AA had measurable plasma levels of IL-6, but plasma levels of IL-1beta were 2.7-fold higher in AA animals. Following LPS injection both IL-1beta and IL-6 increased more markedly in AA than in control rats. Neither controls nor AA rats expressed IL-1beta or IL-6 mRNA in the brain. However, following LPS these were induced in the subfornical organ, choroid plexus, and median eminence of both groups of animals. The areas expressing IL-1b mRNA were larger in the AA animals and exhibited a punctate pattern throughout the brain parenchyma and PVN. These data reveal an increased peripheral and central immunological response to LPS during the chronic inflammatory process of AA, providing a mechanism through which inflammatory disease can influence the response to a novel immunological challenge.
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PMID:Hypothalamic pituitary adrenal axis and immune responses to endotoxin in rats with chronic adjuvant-induced arthritis. 1246 Jun 13

A somnogenic function is suspected for various cytokines. Foregoing experiments in humans indicated a selective increase in the production of interleukin-2 (IL-2) during sleep as compared with nocturnal wakefulness. Here, we examined whether conversely, IL-2 exerts a promoting influence on sleep. Also, the effects of IL-2 administered at ultra-low doses on systemic immune and endocrine parameters were assessed. Eighteen healthy men participated in three night sessions, receiving subcutaneously at 19:00 h either placebo or recombinant human IL-2 at doses of 1000 and 10,000 IU/kg bw. Polysomnographical recordings were obtained between 23:00 and 07:00 h. Blood was collected repeatedly to determine (i) white blood cell (WBC) counts including the enumeration of monocytes, natural killer (NK) cells, and lymphocyte subsets, (ii) serum concentrations of IL-2, soluble IL-2 receptor (sIL-2r), IL-4, IL-6, and interferon-gamma (IFN-gamma), and (iii) concentrations of adrenocorticotropin (ACTH), cortisol, thyreotropin (TSH), and growth hormone (GH). Changes after 1000 IU/kg bw IL-2 generally remained non-significant. However, distinct effects occurred after 10,000 IU/kg bw IL-2, inducing serum IL-2 concentrations selectively activating the high affinity IL-2 receptor. At this dose, IL-2 reduced the number of circulating lymphocytes (including all major subtypes) and NK cells, while counts of monocytes and neutrophils were increased. IL-4 release was stimulated and IFN-gamma concentration reduced after IL-2. Also, IL-2 increased the TSH concentration. There were no hints at a sleep promoting effect of IL-2. Immune changes suggest that nocturnal IL-2 administration induces a shift towards Th2 mediated defense.
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PMID:Systemic immune parameters and sleep after ultra-low dose administration of IL-2 in healthy men. 1248 Apr 97

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

It is well established that the hypothalamic-pituitary-adrenal responses to immune stressors are sexually dimorphic in rodents (females > males), but the underlying mechanism is still unclear. To investigate the mechanism, in this study we examined whether the sex steroid environment affects the following variables in male and female rats: (1) plasma levels of ACTH, interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) after systemic lipopolysaccharide (LPS) administration; (2) static concentrations of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in the mediobasal hypothalamus (MBH) and those of ACTH in the anterior pituitary (AP); and (3) the binding characteristics of IL-1beta, IL-6 and TNF-alpha in the MBH and AP. LPS-induced ACTH release was significantly higher in female than in male rats, and this sexual difference was abolished by performing gonadectomy in both sexes. Administration of physiological doses of testosterone and oestradiol to gonadectomized males and females, respectively, restored the altered ACTH responses to normal. Changes in the sex steroid milieu did not affect plasma cytokine responses to LPS, tissue contents of CRH, AVP and ACTH, or the IL-6 binding characteristics in the MBH and AP. However, the number of IL-1beta and TNF-alpha binding sites, but not their binding affinities, in the MBH showed significant changes according to altered sex hormone milieu, in the same direction as the LPS-induced ACTH response. These results suggest that the hypothalamic sensitivity to peripheral IL-1beta and TNF-alpha may be an important mechanism underlying the sexually dimorphic ACTH response to LPS in rats.
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PMID:A mechanism underlying the sexually dimorphic ACTH response to lipopolysaccharide in rats: sex steroid modulation of cytokine binding sites in the hypothalamus. 1256 59

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

The purpose of this study was to investigate the relationship between the plasma leptin level and clinical parameters in patients with burn injury. Six patients with burn injury were admitted to the Emergency and Critical Care Medicine Center of St. Marianna University Hospital within 1h after injury. Plasma levels were monitored for leptin, proinflammatory cytokines (interleukin (IL)-1 beta, IL-6, tumor necrosis factor alpha (TNF alpha)), stress-related parameters (adrenocorticotropic hormone (ACTH), cortisol, and C-reactive protein (CRP)). The change in individual plasma leptin levels did not show similar pattern in all these patients. However, leptin levels remained within the normal range, except in a patient (Case 1) complicated with severe hypovolemic shock. Plasma ACTH and cortisol levels were also elevated in most of the patients. Examination of relationships among plasma leptin, proinflammatory cytokines, and stress-related parameters revealed a significant positive correlation between the plasma leptin level and IL-1 beta or IL-6. These results suggest that the plasma leptin level may have some relations to plasma proinflammatory cytokines in pathophysiologic responses to critical conditions of burn injury.
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PMID:Plasma leptin levels in patients with burn injury: a preliminary report. 1288 Jul 24


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