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)

Opioids are known to suppress a number of elements of the immune response, including antimicrobial resistance, antibody production, and delayed-type hypersensitivity. Phagocytic cells may be particularly susceptible to opioid administration, since reduced production of the cytokines IL-1, IL-6 and TNF-alpha, monocyte-mediated phagocytosis, and both neutrophil and monocyte chemotaxis have all been well established. Earlier studies have shown that both mu- and delta-opioid agonists induce a chemotactic response in monocytes and neutrophils. In addition, mu- and delta-opioid administration inhibited the chemotactic response of these cell populations to a number of chemokines through a process of heterologous desensitization. We report here that mu-, delta-, and kappa-opioid agonists also induce a chemotactic response in T lymphocytes. Using the human T-cell line Jurkat, we have confirmed previous observations that pre-incubation with met-enkephalin (MetEnk), an endogenous opioid agonist, prevents the subsequent chemotactic response to the chemokine RANTES. On the other hand, treatment with MetEnk does not alter the response to the chemokine SDF-1 alpha. Moreover, we found that pre-treatment with RANTES prevented a subsequent response of monocytes to the mu-opioid agonist DAMGO. These results suggest that activation of members of the opioid and chemokine receptor families leads to downregulation of each other's leukocyte migratory activities.
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PMID:Bidirectional heterologous desensitization of opioid and chemokine receptors. 1126 44

Interleukin (IL)-6 is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis on all levels in humans, and appears to play a pathogenic role in conditions related to chronic stress and physiological ageing; with physiological ageing showing a similar hormonal and immunological pattern to chronic stress. IL-6 and its receptor IL-6R are co-expressed at similar sites in the human adrenal gland, which seems to be an important source of IL-6 production. In vitro, in primary cultures of adrenal gland cells, chronic exposure to IL-6 stimulates adrenocortical steroid release in a time- and dose-dependent manner. This explains the high systemic cortisol levels in the absence of adequate plasma concentrations of corticotropin (ACTH) observed in patients after long-term treatment with IL-6. It could therefore be concluded that in situations of prolonged stress, when corticotropin-releasing hormone and ACTH release are suppressed by feedback inhibition due to circulating glucocorticoids, IL-6 maintains the elevated glucocorticoid levels by direct stimulation of adrenocortical steroidogenesis via autocrine/paracrine mechanisms.
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PMID:The role of interleukin-6 in the human adrenal gland. 1128 77

Gram-negative bacteria-derived lipopolysaccharide (LPS or endotoxin) is known to play an important role in immune and neurological manifestations during bacterial infections. LPS exerts its effects through cytokines, and peripheral or brain administration of LPS activates cytokine production in the brain. In this study, we investigated cytokine and neuropeptide mRNA profiles in specific brain regions and peripheral organs, as well as serum tumor necrosis factor (TNF)-alpha protein levels, in response to the intraperitoneal administration of LPS. For the first time, the simultaneous analysis of interleukin (IL)-1beta system components (ligand, signaling receptor, receptor accessory proteins, receptor antagonist), TNF-alpha, transforming growth factor (TGF)-beta1, glycoprotein 130 (IL-6 receptor signal transducer), OB protein (leptin) receptor, neuropeptide Y, and pro-opiomelanocortin (opioid peptide precursor) mRNAs was done in samples from specific brain regions in response to peripherally administered LPS. The same brain region/organ sample was assayed for all cytokine mRNA components. Peripherally administered LPS up-regulated pro-inflammatory cytokine (IL-1beta and/or TNF-alpha) mRNAs within the cerebral cortex, cerebellum, hippocampus, spleen, liver, and adipose tissue. LPS also increased plasma levels of TNF-alpha protein. LPS did not up-regulate inhibitory (anti-inflammatory) cytokine (IL-1 receptor antagonist and TGF-beta1) mRNAs in most brain regions (except for IL-1 receptor antagonist in the cerebral cortex and for TGF-beta1 in the hippocampus), while they were increased in the liver, and IL-1 receptor antagonist was up-regulated in the spleen and adipose tissue. Overall, peripherally administered LPS modulated the levels of IL-1beta system components within the brain and periphery, but did not affect the neuropeptide-related components studied. The data suggest specificity of transcriptional changes induced by LPS and that cytokine component up-regulation in specific brain regions is relevant to the neurological and neuropsychiatric manifestations associated with peripheral LPS challenge.
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PMID:Pro-inflammatory and anti-inflammatory cytokine mRNA induction in the periphery and brain following intraperitoneal administration of bacterial lipopolysaccharide. 1130 98

Aging is accompanied by marked changes of steroid hormone levels which vary among women and men. The age-related increase of cytokines such as interleukin (IL)- 6 may modulate the endocrine system. We aimed to investigate the role of IL-6 for the gender-specific changes of acrophase steroid hormone secretion in healthy subjects during aging. Out of 120 healthy subjects, 60 men and 48 women (non luteal phase) were recruited (age: 18 to 75 years). Age was positively correlated with IL-6 (female and male: p<0.001) and adrenocorticotropic hormone (ACTH) in women only (p<0.001). Age was negatively correlated with progesterone (female and male: p<0.001), cortisol (only female: p=0.003), androstenedione (female and male: p<0.001), but not 17OH progesterone. After correction for IL-6, the age-related decrease of steroid hormones was blunted in both gender groups except for androstenedione (female and male: p<0.005). Furthermore, the ratio of serum cortisol to plasma ACTH decreased with age only in women but not in men (female: p< 0.001). Correction for IL-6 did not markedly change the negative interrelationship between age and the mentioned ratio in these women. However, a linear regression analysis revealed that the increase of ACTH in relation to cortisol depends on serum free testosterone in men (p=0.042) and on serum free 17 beta-estradiol (p<0.001) together with serum IL-6 in women (p=0.021). In conclusion, IL-6 plays an important role for acrophase pituitary and peripheral hormone secretion in women only. The gender-specific changes of cortisol in relation to ACTH depend on the age-related decrease of the respective sex hormone in both gender groups and the increase of IL-6 in women. This study underlines the hormone-like role of IL-6 in the aging process of the endocrine system in women.
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PMID:Differential age-related changes of hypothalamus - pituitary - adrenal axis hormones in healthy women and men - role of interleukin 6. 1134 5

The aim of the present study was to examine the role of opiate receptor activation in modulating the hemodynamic, neuroendocrine, and tissue (lung and spleen) cytokine responses to fixed pressure (40 mm Hg) hemorrhage. Chronically catheterized, conscious unrestrained non-heparinized male Sprague-Dawley rats were pretreated with either naltrexone (15 mg/kg intraperitoneally in 0.5 mL of saline) or saline (0.5 mL) 15 min prior to hemorrhage followed by fluid resuscitation with Ringer's lactate. Animals were sacrificed at completion of the 60-min resuscitation period. Blood loss required to achieve mean arterial blood pressure (MABP) of 40 mm Hg was higher in naltrexone-treated animals than in time-matched saline controls (4.4+/-0.2 versus 3.7+/-0.2 mL/100 g BW, P< 0.05). Hemorrhage increased plasma levels of corticosterone (30%) and ACTH (3-fold) within 15 min. Naltrexone prevented the hemorrhage-induced rise in corticosterone without affecting the rise in ACTH. Hemorrhage increased beta-endorphin levels (4-fold) and produced an immediate (5 min) and progressive increase in circulating epinephrine and norepinephrine levels reaching values that were 50- and 20-fold, respectively, higher than basal. Pre-treatment with naltrexone did not alter the time course or magnitude of the hemorrhage-induced increases in plasma beta-endorphin or catecholamines. Hemorrhage increased lung and spleen content of TNF (60%), IL-1alpha (300%), IL-6 (40%-60%), and IL-10 (80%) above values of time-matched sham control animals. Pre-treatment with naltrexone blunted the magnitude of the increases in tissue cytokine content in response to a given blood loss. These results indicate that endogenous opiates modulate the hemodynamic instability, neuroendocrine, and cytokine responses to hemorrhagic shock.
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PMID:Opiate modulation of hemodynamic, hormonal, and cytokine responses to hemorrhage. 1138 21

Previous studies have shown that the same stressor, depending on intensity, controllability, or duration, can have different effects on the immune system. The purpose of this study was to determine the effect of 10- and 20-min rotation on natural killer (NK) cell activity and also to establish if changes in body temperature, proinflammatory cytokine (IL-1beta, IL-6, and TNF-alpha) levels, and proopiomelanocortin (POMC)-derived peptide (ACTH and beta-endorphin) levels parallel the changes in NK cell activity in mice. We found that 10-min rotation significantly increased NK cell activity as compared to both the control (home cage) group and the 20-min-rotation group, while NK cell activity in the 20-min group was not significantly changed compared to the control group. Both 10 and 20 min of rotational stress decreased body temperature and induced significant changes in the proinflammatory cytokine and POMC-derived peptide levels as compared to the control group. The pattern of proinflammatory cytokine expression was quite different between the 10- and 20-min rotation groups. All three proinflammatory cytokines were expressed sequentially (at 0 h after rotation TNF-alpha, at 6 h IL-1beta and IL-6, and at 24 h IL-6) in the 10-min rotation group, while the 20-min rotation group had a small increase in IL-1beta (6.7 +/- 1.8 pg/ml) at 0 h and increased levels of IL-6 at 6 and 24 h. There was a dissociation of ACTH and beta-endorphin expression in both groups resulting in significantly more beta-endorphin (p < 0.05) in the 10-min group at 6 h and significantly more ACTH (p < 0.04) in the 20-min group at 6 h. IL-1beta and beta-endorphin have both been shown to have a direct stimulatory effect on NK cell activity. Therefore, we suspect that the significant increase in both IL-1beta and beta-endorphin at 6 h in the 10-min-rotation group may be involved in the increased NK cell activity observed at 24 h in the 10-min-rotation group.
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PMID:Effects of rotational stress of different duration on NK cell activity, proinflammatory cytokines, and POMC-derived peptides in mice. 1143 50

The effects of chronic immune challenge on cytokine expression and hypothalamic-pituitary-adrenal axis (HPA) axis responses to stress were studied in Wistar rats after administration of increasing doses of lipopolysaccharide (LPS). Repeated LPS (R-LPS) decreased body weight and increased adrenal weight and pituitary pro-opiomelanocortin mRNA levels. LPS injection increased plasma adrenocorticotropic hormone (ACTH) and corticosterone but the effect was attenuated in R-LPS. Plasma corticosterone but not ACTH responses to restraint were also reduced in R-LPS. Basal and restraint-stimulated corticotropin releasing hormone (CRH) mRNA levels were lower in R-LPS, but responses to a new LPS injection were similar to controls. In contrast, type 1 CRH receptor (CRH-R1) mRNA responses to both LPS and restraint were blunted in R-LPS. Vasopressin mRNA levels in parvocellular neurones were higher in R-LPS, and increased further after restraint but not after a new LPS injection. Glucocorticoid receptor (GR) levels in the paraventricular nucleus (PVN) increased after a single LPS or R-LPS (24 h after the last injection) but declined after a new injection in R-LPS. Interleukin (IL)-1beta and IL-6 mRNAs increased in the pituitary, spleen and circumventricular organs after single or R-LPS, suggesting that cytokines may contribute to the activation of the HPA axis though pathways from the circumventricular organs as well as paracrine effects in the pituitary. The data show that (i) adaptation of the HPA axis during repeated LPS injection involves increases in vasopressin : CRH expression ratios in parvocellular neurones; (ii) that hypothalamic CRH and vasopressin responses to acute stimulation are independent of CRH-R1 expression in the PVN; and (iii) there is a dissociation between pituitary and adrenal responses to acute stress suggesting a decrease of adrenal sensitivity to ACTH.
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PMID:Effect of repeated lipopolysaccharide administration on tissue cytokine expression and hypothalamic-pituitary-adrenal axis activity in rats. 1148 88

Preterm delivery (PTD) appears to be a complex trait determined by both genetic and environmental factors. Few studies have examined genetic influence on PTD. The overall goal of our study is to examine major candidate genes of PTD and to test gene-environment interactions. Our study includes 500 preterm trios, including 500 preterm babies and their parents and 500 maternal age-matched term controls. We will perform the transmission/disequilibrium test (TDT) on candidate genes thought to be important in each of the four biological pathways of PTD: (1) decidual chorioamionotic inflammation: interleukin 1 (IL-1), IL-6, and tumour necrosis factor (TNF); (2) maternal and fetal stress: corticotropin-releasing hormone (CRH); (3) uteroplacental vascular lesions: methylenetereahydrofolate reductase (MTHFR); and (4) susceptibility to environmental toxins: GSTM1, GSTT1, CYP1A1, CYP2D6, CYP2E1, NAT2, NQO1, ALDH2, and EPHX. We will also perform standard case-control analyses on the 500 preterm cases and 500 term controls to examine gene-environment interactions. The major environmental, nutritional and social factors as well as clinical variables known or suspected to be associated with PTD will be used to test for gene-environment interactions. This study integrates epidemiological and clinical data as well as genetic markers along major pathogenic pathways of PTD. The findings from this study should improve our understanding of genetic influences on PTD and gene-environment interactions.
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PMID:Molecular epidemiology of preterm delivery: methodology and challenges. 1152 Apr 1

Stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by proinflammatory cytokines results in increased release of glucocorticoid that restrains further development of the inflammatory process. IL-6 has been suggested to stimulate the HPA axis during immune activation independent of the input of hypothalamic corticotropin-releasing hormone (CRH). We used the corticotropin-releasing hormone-deficient (Crh(-/-)) mouse to elucidate the effect of CRH deficiency on IL-6 expression and IL-6-induced HPA axis activation during turpentine-induced inflammation. We demonstrate that during inflammation CRH is required for a normal adrenocorticotropin hormone (ACTH) increase but not for adrenal corticosterone rise. The paradoxical increase of plasma IL-6 associated with CRH deficiency suggests that IL-6 release during inflammation is CRH-dependent. We also demonstrate that adrenal IL-6 expression is CRH-dependent, as its basal and inflammation-induced expression is blocked by CRH deficiency. Our findings suggest that during inflammation, IL-6 most likely compensates for the effects of CRH deficiency on food intake. Finally, we confirm that the HPA axis response is defective in Crh(-/-)/IL-6(-/-) mice. These findings, along with the regulation of IL-6 by CRH, support the importance of the interaction between the immune system and the HPA axis in the pathophysiology of inflammatory diseases.
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PMID:Corticotropin-releasing hormone regulates IL-6 expression during inflammation. 1160 23

This prospective observational study investigated the relationship of the hypothalamic-pituitary-adrenal axis to inflammatory markers and to disease severity in children with meningococcal disease. In total, 32 children were studied: 10 with distinct meningococcal meningitis (MM), 10 with MM and septic shock, and 12 with fulminant meningococcal septicemia (FMS). Levels of adrenocorticotropic hormone (ACTH) and interleukin (IL)-6, IL-8, and IL-10 were lowest in the MM group and dramatically elevated in the FMS group. Cortisol and C-reactive protein levels were highest in the MM group and relatively low in the FMS group. Levels of ACTH and inflammatory markers decreased within the first 24 h of admission, but cortisol levels did not fluctuate. Cortisol was significantly inversely correlated with IL-6, IL-8, and IL-10 (P < or =.04). These results suggest that the adrenal reserve in children is insufficient to handle the extreme conditions and stress associated with severe meningococcal disease.
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PMID:Adrenocorticotropic hormone and cortisol levels in relation to inflammatory response and disease severity in children with meningococcal disease. 1174 Jul 28


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