UNIPROT:P05231 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diagnosis of early-onset neonatal infection has led to the development of several screening tests including C-reactive protein, a very commonly used marker, and cytokines (mainly interleukin-6 and -8), alone or in combination with C-reactive protein, based on the premise that their increases in response to infection may precede that of C-reactive protein. In recent years the search for diagnostic tests has turned to procalcitonin, a propeptide of calcitonin, which appears to be a promising marker of infection in newborn infants. Additionally, specific leukocyte cell surface antigens (mainly CD11b and CD64), detected by flow cytometry, are evaluated as markers of neonatal infection, since their expression on the cell membrane increases in substantial quantities after leukocyte activation by bacteria or their cellular products. This review aims to examine the role of these newly available immunologic indices and to assess their validity as diagnostic markers of infection during the neonatal period.
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PMID:Immunologic markers in the neonatal period: diagnostic value and accuracy in infection. 1583 52

Mast cells are critical players in allergic reactions, but they have also been shown to be important in immunity and recently also in inflammatory diseases, especially asthma. Migraines are episodic, typically unilateral, throbbing headaches that occur more frequently in patients with allergy and asthma implying involvement of meningeal and/or brain mast cells. These mast cells are located perivascularly, in close association with neurons especially in the dura, where they can be activated following trigeminal nerve, as well as cervical or sphenopalatine ganglion stimulation. Neuropeptides such as calcitonin gene-related peptide (CGRP), hemokinin A, neurotensin (NT), pituitary adenylate cyclase activating peptide (PACAP), and substance P (SP) activate mast cells leading to secretion of vasoactive, pro-inflammatory, and neurosensitizing mediators, thereby contributing to migraine pathogenesis. Brain mast cells can also secrete pro-inflammatory and vasodilatory molecules such as interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), selectively in response to corticotropin-releasing hormone (CRH), a mediator of stress which is known to precipitate or exacerbate migraines. A better understanding of brain mast cell activation in migraines would be useful and could lead to several points of prophylactic intervention.
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PMID:The role of mast cells in migraine pathophysiology. 1596 Sep 87

The pain related peptide, calcitonin gene-related peptide (CGRP), plays an important role in inflammatory pain and immune responses. However, its role in neuropathic pain is not established. Following nerve injury, CGRP and pro-inflammatory interleukin-6 (IL-6) are increased in injured nerves. The aim of this study was to determine if CGRP in injured nerves is involved in the up-regulation of IL-6 and in the maintenance of neuropathic pain. Perineural injection of a neutralizing IL-6 antiserum or CGRP receptor antagonists (CGRP8-37 and BIBN4096BS) effectively attenuated thermal hyperalgesia 4 weeks after partial sciatic nerve ligation. Perineural CGRP antagonists also dramatically reduced IL-6 level in injured nerves. CGRP release from injured sites was dramatically increased and CGRP immunoreactivity was localized in both neuroma and invading macrophages. CGRP receptor markers (CRLR and RAMP1) were expressed in invading macrophages. Both CGRP antagonists significantly reduced IL-6 release from injured nerve explants. In cell cultures derived from injured nerves, CGRP concentration-dependently increased IL-6 release, an effect also blocked by CGRP antagonists. Taken together, these data show that increased levels of CGRP in injured neuroma and invading macrophages are involved in the up-regulation of IL-6 in macrophages as well as in the maintenance of neuropathic pain.
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PMID:Increased calcitonin gene-related peptide in neuroma and invading macrophages is involved in the up-regulation of interleukin-6 and thermal hyperalgesia in a rat model of mononeuropathy. 1680 7

During neuronal-induced inflammation, mast cells may respond to stimuli such as neuropeptides in an FcepsilonRI-independent manner. In this study, we characterized human mast cell responses to substance P (SP), nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) and compared these responses to human mast cell responses to immunoglobulin E (IgE)/anti-IgE and compound 48/80. Primary cultured mast cells, generated from CD34(+) progenitors in the presence of stem cell factor and interleukin-6 (IL-6), and human cultured mast cells (LAD2) were stimulated with these and other stimuli (gastrin, concanavalin A, radiocontrast media, and mannitol) and their degranulation and chemokine production was assessed. VIP and SP stimulated primary human mast cells and LAD cells to degranulate; gastrin, concanavalin A, radiocontrast media, mannitol, CGRP and NGF did not activate degranulation. While anti-IgE stimulation did not induce significant production of chemokines, stimulation with VIP, SP or compound 48/80 potently induced production of monocyte chemoattractant protein-1, inducible protein-10, monokine induced by interferon-gamma (MIG), RANTES (regulated on activation, normal, T-cell expressed, and secreted) and IL-8. VIP, SP and compound 48/80 also activated release of tumour necrosis factor, IL-3 and granulocyte-macrophage colony-stimulating factor, but not IL-4, interferon-gamma or eotaxin. Human mast cells expressed surface neurokinin 1 receptor (NK1R), NK2R, NK3R and VIP receptor type 2 (VPAC2) but not VPAC1 and activation of human mast cells by IgE/anti-IgE up-regulated expression of VPAC2, NK2R, and NK3R. These studies demonstrate the pattern of receptor expression and activation of mast cell by a host of G-protein coupled receptor ligands and suggest that SP and VIP activate a unique signalling pathway in human mast cells. These results are likely to have direct relevance to neuronally induced inflammatory diseases.
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PMID:Neuropeptides activate human mast cell degranulation and chemokine production. 1792 33

Neuropathic pain is generally resistant to "classical" analgesic drugs, including opioids, and there is still an urgent need for really effective treatments to alleviate pain caused by lesions of the peripheral and/or central nervous system. The pathophysiological mechanisms underlying neuropathic pain are still poorly known, and treatments are mainly empirical. Antidepressant drugs are generally prescribed first, with positive but limited results in a significant proportion of patients. Anticonvulsant drugs (carbamazepine, phenytoin, lamotrigine) are also used but are often poorly tolerated. Clinical studies and preclinical investigations support the idea that the nature of neuropathic pain, and the underlying mechanisms, are different in the cephalic (trigeminal) territories and the extracephalic (spinal) territories. In order to further investigate these regional differences, we used rat nerve ligature models. Comparison of allodynia/hyperalgesia in the vibrissal territory caused by unilateral ligature of the infraorbital nerve (2nd branch of the trigeminal nerve) with those in the hindpaw ipsilateral to unilateral ligature of the sciatic nerve revealed marked differences in their responses to sodium channel blockers (such as tetrodotoxin), serotonin (5-HT) receptor agonists and calcitonin gene-related peptide (CGRP) receptor antagonists. In particular, 5-HT7 receptor agonists were particularly effective at reducing allodynia in sciatic nerve-ligated rats, but were completely ineffective in infraorbital nerve-ligated rats. Conversely, triptans (5-HT1B/1D receptor agonists) and CGRP-receptor antagonists markedly inhibited cephalic allodynia in infraorbital nerve-ligated rats but failed to relieve neuropathic pain in sciatic nerve-ligated animals. Interestingly, ligature-induced expression of the proinflammatory cytokine interleukin-6 in central tissues showed marked differences in sciatic nerve- and infraorbital nerve-ligated rats, providing direct evidence of differences in the mechanisms underlying extra-cephalic- and cephalic neuropathic pain. Such preclinical studies should contribute to the design of innovative strategies for more effective and well-tolerated treatments for neuropathic pain in cephalic and extra-cephalic territories.
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PMID:[Neuropathic pain. Physiopathological mechanisms and therapeutic perspectives]. 1923 82

Lactoferrin (LF) is reported to stimulate osteoblast proliferation and inhibit osteoclast activity in bone cell culture. However, the effect of oral LF on bone in osteoporosis needs to be explored. Three-month-old female Sprague-Dawley rats (n = 70) were assigned to the following groups: sham-operated, ovariectomized (OVX) untreated, OVX + bovine serum albumin (BSA; 85 mg/kg body weight), OVX + LF (0.85 mg/kg, 8.5 mg/kg, and 85 mg/kg body weight), and OVX + 17beta-estradiol (E(2); 10 microg/kg body weight). After 3 mo of treatment, E(2) completely prevented the OVX-induced bone loss. OVX rats treated with LF were protected against the OVX-induced reduction of bone volume, trabecular number, and thickness, and the elevation of trabecular separation was prevented. LF also increased bone mineral density and increased the parameters of mechanical strength at 8.5- and 85-mg/kg doses. Greater bone formation and reduced bone resorption, as assessed by biochemical markers of bone remodeling, occurred in rats administered LF. LF at 8.5- and 85-mg/kg concentrations caused a significant decrease in serum calcium, but this reduction did not occur in rats fed 0.85 mg/kg LF. In addition, serum tumor necrosis factor-alpha and interleukin-6 production were suppressed and serum calcitonin was elevated significantly in LF-fed rats at all 3 doses. These findings indicated that oral LF not only preserved bone mass but also improved bone microarchitecture. The absorption of LF peptides and their effects on bone cells could to some extent account for the osteogenic function of oral LF.
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PMID:Orally administered lactoferrin preserves bone mass and microarchitecture in ovariectomized rats. 1932 77

Pulsed electromagnetic fields (PEMF) have been used widely to treat nonunion fractures and related problems in bone healing, as a biological and physical method. With the use of Helmholtz coils and PEMF stimulators to generate uniform time-varying electromagnetic fields, the effects of extremely low frequency electromagnetic fields on bone mineral density (BMD) and local factor production in disuse osteoporosis (DOP) rats were investigated. Eighty 4-month-old female Sprague Dawley (SD) rats were randomly divided into intact (INT) group, DOP group, calcitonin-treated (CT) group, and PEMF stimulation group. The right hindlimbs of all the rats were immobilized by tibia-tail fixation except for those rats in the INT group. Rats in the CT group were injected with calcitonin (2 IU/kg, i.p., once a day) and rats in the PEMF group were irradiated with PEMF immediately postoperative. The BMD, serum transforming growth factor-beta 1 (TGF-beta1), and interleukin-6 (IL-6) concentration of the proximal femur were measured 1, 2, 4, and 8 weeks after treatment. Compared with the CT and DOP groups, the BMD and serum TGF-beta1 concentration in the PEMF group increased significantly after 8 weeks. The IL-6 concentration in the DOP group was elevated significantly after operation. The PEMF group showed significantly lower IL-6 level than the DOP group. The results found demonstrate that PEMF stimulation can efficiently suppress bone mass loss. We, therefore, conclude that PEMF may affect bone remodeling process through promoting TGF-beta1 secretion and inhibiting IL-6 expression.
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PMID:Pulsed electromagnetic fields stimulation affects BMD and local factor production of rats with disuse osteoporosis. 1967 Apr 10

Temporomandibular joint (TMJ) pain has been reported to last for prolonged periods in humans. In rodents a variety of methods have been used to measure TMJ nociception, but for most of these methods the period of measurement has been minutes to a couple of hours. In addition, most measurement protocols required restraint or training of the animal. Previous studies from our laboratory demonstrated that feeding behavior, particularly meal duration, was an indicator of TMJ nociception in unrestrained and untrained male and female Sprague-Dawley rats for up to two days. In this study, we first found that injection of complete Freund's adjuvant (CFA) into the TMJ of rats significantly lengthened meal duration for 19 days and also decreased meal frequency for 42 days. Interestingly, the meal duration varied significantly from day to day within the 19 day period. TMJ interleukin-1 beta (IL-1 beta) and calcitonin gene-related peptide (CGRP) were significantly elevated in the TMJ tissues of CFA-injected animals and the level of these markers was attenuated as the meal duration decreased with time. Control animals injected with saline into the TMJ or CFA into the knee did not show a significant lengthening in meal duration but did show a decrease in meal frequency. In a second study, DBA/1LacJ mice given TMJ CFA injections showed a significantly lengthened meal duration on four of the seven days measured using end-of-the meal definition of 5 or 10 min. No other meal pattern changed significantly. Two days post-CFA injection, the DBA/1LacJ mice showed significantly elevated interleukin-6 (IL-6), but not elevated IL-1 beta. Seven days post-injection, both IL-6 and IL-1 beta were significantly elevated. No change in CGRP was detected. In this study C57Bl/6 mice also received TMJ CFA injections, but they did not show a lengthening in any meal pattern or significant increases in IL-1 beta, IL-6 or CGRP. Our data show, for the first time, that meal duration can be used to measure CFA-induced nociception in the TMJ over the course of several weeks in unrestrained rats and for up to seven days in the DBA/1LacJ mouse strain. In addition, C57Bl/6 mice are resistant to CFA-induced TMJ nociception at the same dose used in the DBA/1LacJ mice.
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PMID:Measuring persistent temporomandibular joint nociception in rats and two mice strains. 2015 46

Sickle cell disease causes severe pain. We examined pain-related behaviors, correlative neurochemical changes, and analgesic effects of morphine and cannabinoids in transgenic mice expressing human sickle hemoglobin (HbS). Paw withdrawal threshold and withdrawal latency (to mechanical and thermal stimuli, respectively) and grip force were lower in homozygous and hemizygous Berkley mice (BERK and hBERK1, respectively) compared with control mice expressing human hemoglobin A (HbA-BERK), indicating deep/musculoskeletal and cutaneous hyperalgesia. Peripheral nerves and blood vessels were structurally altered in BERK and hBERK1 skin, with decreased expression of mu opioid receptor and increased calcitonin gene-related peptide and substance P immunoreactivity. Activators of neuropathic and inflammatory pain (p38 mitogen-activated protein kinase, STAT3, and mitogen-activated protein kinase/extracellular signal-regulated kinase) showed increased phosphorylation, with accompanying increase in COX-2, interleukin-6, and Toll-like receptor 4 in the spinal cord of hBERK1 compared with HbA-BERK. These neurochemical changes in the periphery and spinal cord may contribute to hyperalgesia in mice expressing HbS. In BERK and hBERK1, hyperalgesia was markedly attenuated by morphine and cannabinoid receptor agonist CP 55940. We show that mice expressing HbS exhibit characteristics of pain observed in sickle cell disease patients, and neurochemical changes suggestive of nociceptor and glial activation. Importantly, cannabinoids attenuate pain in mice expressing HbS.
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PMID:Pain-related behaviors and neurochemical alterations in mice expressing sickle hemoglobin: modulation by cannabinoids. 2065 Oct 80

Pancreatic pain resulting from chronic inflammation of the pancreas is often intractable and clinically difficult to manage with available analgesics reflecting the need for more effective therapies. The mechanisms underlying pancreatitis pain are not well understood. Here, the possibility that interleukin-6 (IL-6) may promote pancreatitis pain was investigated with TB-2-081 (3-O-formyl-20R,21-epoxyresibufogenin, EBRF), a small molecule IL-6 receptor antagonist that was semi-synthetically derived from natural sources. The potential activity and mechanism of TB-2-081 were investigated following the induction of persistent pancreatitis using dibutyltin dichloride (DBTC) in rats. TB-2-081 displaces the binding of IL-6 to the human recombinant soluble IL-6 receptor with apparent high affinity and inhibits IL-6 mediated cell growth. Systemic or oral, but not intrathecal, administration of TB-2-081 reversed DBTC-induced abdominal hypersensitivity in a dose- and time-dependent manner. IL-6 levels were significantly up-regulated in the dorsal root ganglia (DRG) of rats with pancreatitis on day 6 after DBTC injection. IL-6-enhanced capsaicin-evoked release of calcitonin gene-related peptide from cultured DRG neurons was blocked by TB-2-081. Our data demonstrate that TB-2-081 acts as a systemically available and orally active small molecule IL-6 receptor antagonist. TB-2-081 effectively reduces pancreatitis-induced pain through peripheral mechanisms that are likely due to (a) increased expression of IL-6 in the DRG and (b) IL-6-mediated sensitization of nociceptive neurons. The activity of TB-2-081 implicates an important role for IL-6 in sustaining pancreatitis pain. Strategies targeting IL-6 actions through small molecule antagonists may offer novel approaches to improve the therapy of chronic pancreatitis and other chronic pain states.
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PMID:Reversal of pancreatitis-induced pain by an orally available, small molecule interleukin-6 receptor antagonist. 2063 91

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