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)

The anti-inflammatory mechanisms of minocycline, an antibiotic used in the treatment of the inflammatory component of acne, are only partially understood. In addition to inflammation due to cytokines (IL-1, IL-6, TNF-alpha, etc.), recent studies have shown that neuropeptide-mediated neurogenic inflammation may play an important role in cutaneous inflammation. The purpose of this study was to investigate minocycline-induced modulation of cutaneous production of alpha-melanocyte-stimulating hormone (alpha-MSH), a neuropeptide with known anti-inflammatory activity. Two different skin models were used: explants of inflammatory skin and reconstituted skin, both incubated with minocycline at different concentrations and for different time periods. Epidermal production of alpha-MSH, as evaluated by immunofluorescence and immunoperoxidase techniques, showed increased expression in both models. This neuropeptide, which has an anti-inflammatory activity (notably through production of IL-10, antagonism of IL-1 and inhibition of the chemotaxis of polymorphonuclear leukocytes), thus plays a role in the anti-inflammatory action of minocycline.
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PMID:Minocycline modulation of alpha-MSH production by keratinocytes in vitro. 1042 80

Certain functional interactions between the nervous, endocrine, and immune systems are mediated by cytokines. The pro-inflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF) were among the first to be recognized in this regard. A modulator of these cytokines, IL-10, has been shown to have a wide range of activities in the immune system; in this review, we describe its production and actions in the hypothalamic-pituitary-adrenal (HPA) axis. IL-10 is produced in pituitary, hypothalamic, and neural tissues in addition to lymphocytes. IL-10 enhances corticotropin releasing factor (CRF) and corticotropin (ACTH) production in hypothalamic and pituitary tissues, respectively. Further downstream in the HPA axis endogenous IL-10 has the potential to contribute to regulation of glucocorticosteroid production both tonically and following stressors. Our studies and those of others reviewed here indicate that IL-10 may be an important endogenous regulator in HPA axis activity and in CNS pathologies such as multiple sclerosis. Thus, in addition to its more widely recognized role in immunity, IL-10's neuroendocrine activities described here point to its role as an important regulator in communication between the immune and neuroendocrine systems.
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PMID:IL-10 as a mediator in the HPA axis and brain. 1069 24

There is accumulating evidence for a strong interaction between components of the nervous system and the immune system. Accordingly, specific receptors for neuropeptides were found to be expressed on immunocompetent cells and several neuropeptides were recognized as potent regulators of immune and inflammatory reactions. Among various neuropeptides such as substance P, calcitonin gene-related peptide and others alpha-melanocyte-stimulating hormone (alpha-MSH) was found to be produced in the skin. Moreover, melanocortin receptor 1 which is specific for alpha-MSH and ACTH is expressed in the skin on keratinocytes, dendritic cells, macrophages and endothelial cells. In monocytes, macrophages and dendritic cells alpha-MSH inhibits the production and activity of immunoregulatory and proinflammatory cytokines such as IL-2, IFNgamma and IL-1. It downregulates the expression of costimulatory molecules such as CD86 and CD40 and induces the production of suppressor factors such as the cytokine synthesis inhibitory factor IL-10. On endothelial cells alpha-MSH is capable of downregulating the LPS-induced expression of adhesion molecules such as vascular cellular adhesion molecules and E-selectin. Moreover, the LPS-induced activation of transcription factors such as NFkappaB is downregulated by alpha-MSH. In a mouse model intravenous or topical application of alpha-MSH was found to inhibit the induction as well as the effector phase of a contact hypersensitivity reaction and to induce hapten-specific tolerance. Moreover, there is evidence that the N-terminal tripeptide of alpha-MSH is sufficient for its in vitro and in vivo immunomodulatory effects. These findings indicate that the production of immunosuppressing neuropeptides such as alpha-MSH by epidermal cells may play an essential role during the pathogenesis of immune and inflammatory reactions in the skin.
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PMID:alpha-melanocyte-stimulating hormone as a mediator of tolerance induction. 1072 12

Adrenal medullary tissue including chromaffin cells was grafted intrathecally in cancer patients to relieve intractable pain. The central nervous system (CNS) is considered an immune privileged site. Therefore, non-HLA-matched and unencapsulated tissue was grafted in 15 patients and 1 sham control in a series of at least 20 grafts. We observed an increase in CSF lymphocyte counts in 15/20 allografts (75%). In contrast to peripheral blood, CD4 T cells predominated in the CSF, but failed to exhibit an activated phenotype (CD25+ CD45RO+ HLA-DR+). The positive effect of graft on pain, the high met-enkephalin levels, the absence of any increase in CSF cytokine levels particularly for IFN-gamma or IL-2 (but not IL-10 and IL-6), indirectly indicated that the graft was tolerated despite the presence of CSF lymphocytes. The single treatment failure and three of four cases of partial efficacy occurred in grafts where CSF lymphocytes were present. Moreover, when assayed (n = 7), the CD4+ CSF lymphocytes still retained the capacity to exhibit ex vivo a normal or enhanced frequency of T CD4 cells producing IFN-gamma and IL-2. Taken together, our observations indicate that impairment of the local immunosuppressive balance can lead to activation of those CSF CD4 T cells and drive a rejection process. This study suggests further work on the purification and/or the immunoisolation of tissues grafted in the CNS will be necessary, particularly when the possibility of long-term and repeated grafting is considered.
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PMID:Intrathecal grafting of unencapsulated adrenal medullary tissue can bring CD4 T lymphocytes into CSF: a potentially deleterious event for the graft. 1078 70

Neuropeptides and neurohormones have been shown to be able to regulate cutaneous immune reactions. Binding of beta-endorphin (beta-end) on epidermal Langerhans cells (LC) and effects of beta-end on cytokine expression were examined. Biotinylated beta-end bound to the mouse LC-like cell line, XS52, and the binding was replaced with intact beta-end but not with substance P. beta-End augmented secretion of IL-1 beta and IL-10 from XS52 cells were induced by a combination of LPS and GM-CSF. Induction of TNF alpha was suppressed by beta-end. The regulation of cytokine expression was confirmed in fresh LC by RT-PCR. These results suggest that beta-end is a regulator of skin immune function.
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PMID:beta-Endorphin binding and regulation of cytokine expression in Langerhans cells. 1081 76

This review summarizes recent studies on endogenous antipyretic mechanisms. Fever is the result of a balance between pyrogenic and cryogenic cytokines and hormones. Although there is considerable evidence that fever evolved as a host defense response, it is important that the rise in body temperature not be too high. Many endogenous cryogens or antipyretics that limit the rise in body temperature have been identified during the last 25 years. These include alpha-MSH, arginine vasopressin, glucocorticoids, TNF (under certain circumstances), and IL-10. Most recently, evidence has accumulated that cytochrome P-450 (P-450), part of the alternative pathway for arachidonic acid metabolism, plays an important role in reduction of fever and inflammation. Supporting a role for P-450 in endogenous antipyresis and antiinflammation includes evidence that (1) inducers of P-450 reduce fever, (2) inhibitors of P-450 cause a larger fever, (3) and P-450 arachidonic acid metabolites reduce fever.
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PMID:Molecular mechanisms of fever and endogenous antipyresis. 1126 36

Among various neuropeptides such as substance P, calcitonin gene-related peptide and others, alpha-melanocyte-stimulating hormone (alpha-MSH) was found to be produced in the skin. Moreover, melanocortin receptor 1 (MC-1R), which is specific for alpha-MSH and ACTH, is expressed in the skin on keratinocytes, dendritic cells, macrophages and endothelial cells. In monocytes, macrophages and dendritic cells alpha-MSH inhibits the production and activity of immunoregulatory and proinflammatory cytokines such as IL-2, IFN-gamma, TNF-alpha and IL-1. It downregulates the expression of costimulatory molecules such as CD86 and CD40 and induces the production of suppressor factors such as the cytokine synthesis inhibitory factor IL-10. On endothelial cells alpha-MSH is capable of downregulating the LPS-induced expression of adhesion molecules such as vascular cell adhesion molecule (VCAM) and E-selectin. Moreover, the LPS-induced activation of transcription factors such as NF kappa B is downregulated by alpha-MSH. In a mouse model i.v. or topical application of alpha-MSH was found to inhibit the induction phase as well as the effector phase of contact hypersensitivity (CHS) reactions and to induce hapten-specific tolerance. These findings indicate that the production of immunosuppressing neuropeptides such as alpha-MSH by epidermal cells may play an essential role during the pathogenesis of immune and inflammatory reactions in the skin.
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PMID:The role of alpha-MSH as a modulator of cutaneous inflammation. 1126 49

The ocular microenvironment is an extreme example of regional immunity. Within its microenvironment, expression of delayed type hypersensitivity (DTH) is suppressed. This immunosuppression is mediated in part by the constitutive expression of alpha-MSH. Previously we have found that alpha-MSH suppresses the production of IFN-gamma by activated effector T cells. Recently we have found that alpha-MSH can mediate induction of TGF-beta-producing T cells that act as regulatory T cells. This has encouraged us to further examine the potential for alpha-MSH to suppress T cell-mediated inflammation (autoimmune disease) and to regulate lymphokine production by effector T cells. When alpha-MSH was injected i.v. into mice at the time of peak retinal inflammation, the severity of experimental autoimmune uveitis (EAU) was significantly suppressed. Effector T cells activated in vitro in the presence of alpha-MSH proliferated and produced IL-4 and enhanced levels of TGF-beta while their IFN-gamma and IL-10 production was suppressed. The alpha-MSH-treated T cells functioned as regulatory T cells by suppressing in vitro IFN-gamma production by other inflammatory T cells. This regulatory activity was the function of alpha-MSH-treated CD4+ CD25+ T cells. Therefore, alpha-MSH mediates immunosuppression by inducing a differential expression of lymphokine production and by inducing activation of regulatory functions in T cells. This implies that alpha-MSH may take part in regional mechanisms of immunosuppression and possibly peripheral tolerance. Thus, alpha-MSH can be used to suppress autoimmune disease and possibly reestablish tolerance to autoantigens.
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PMID:Neuropeptide regulation of immunity. The immunosuppressive activity of alpha-melanocyte-stimulating hormone (alpha-MSH). 1126 50

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

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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