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)

Though opioid receptors are more difficult to purify and characterize than other cell surface receptors, significant progress has been made in the past several years. At least a dozen groups have now reported purification of opioid-binding proteins, either in a form that retains ligand-binding properties, or in a covalently bound form. Although there are some discrepancies in the molecular weights of these proteins, it is significant that many investigators have reported a molecular weight of about 60 kd for the receptor, regardless of whether it is of the mu, delta, or kappa type. This finding, together with immunological evidence, suggests that different opioid receptor types may be highly similar, and could conceivably even share a common ligand-binding subunit. Several groups have prepared monoclonal or polyclonal antibodies to purified opioid-binding proteins, which should be useful in mapping the brain regional distribution of the opioid receptors, determining the regions in the peptide involved in ligand binding and association with second messengers, and in determining the relationships among different opioid receptor types. One group has in fact already established an antigenic similarity between a mu-selective opioid-binding protein in mammalian brain, and the delta opioid receptor in NG108-15 neuroblastoma-glioma hybrid cells. One group has reported cloning of the cDNA for a purified opioid-binding protein. Somewhat surprisingly, its predicted amino acid sequence places it in the immunoglobulin superfamily, with strongest homologies to cell-adhesion molecules such as N-CAM. MAG, amalgam and fasciclin II, as well as receptors for peptides such as PDGF and interleukin-6. However, this is consistent with evidence that opioids can modulate cell-cell interactions of monocytes, and provides further support for links between opioids and the immune system. The second messengers mediating opioid actions are still unknown. Opioid agonists affect the activity of adenylate cyclase and ion channels in some tissues, but neither has been shown to mediate opioid analgesia. The sequence homologies of the purified opioid-binding protein OBCAM with tyrosine kinase growth factor receptors suggest additional possibilities for second messengers.
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PMID:Molecular characterization of opioid receptors. 216 Jul 90

Serum concentrations of the cytokine, interleukin-6 (IL-6), increase after surgical trauma. IL-6 mediates the synthesis of acute phase proteins and stimulates secretion of pituitary hormones. We have examined the time course of circulating IL-6, and cortisol and growth hormone responses in patients undergoing hysterectomy to determine if IL-6 contributes to the early pituitary hormone changes found during surgery. One group (n = 8) received a standardized general anaesthetic while the remaining patients (n = 8) received extradural analgesia to T4-S5 in addition to a similar general anaesthetic. In the general anaesthesia group, there was a significant increase in serum cortisol and growth hormone concentrations before any changes in IL-6 were detected. Furthermore, in the extradural group, in whom these hormonal responses were attenuated, circulating IL-6 concentrations did not differ significantly from the general anaesthesia group. There were no significant differences between the groups in the acute phase response, as measured by circulating concentrations of C-reactive protein and zinc, but the expected effects of extradural block on circulating metabolites and white cell count were demonstrated. We conclude that IL-6 is unlikely to contribute to the initial increases in secretion of pituitary hormones found during surgery, but a later effect of the cytokine on endocrine responses cannot be excluded.
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PMID:Effects of extradural anaesthesia on interleukin-6 and acute phase response to surgery. 751 May 10

In a double-blind, placebo-controlled study, the non-steroidal anti-inflammatory drug, piroxicam, in combination with alfentanil given in a patient-controlled analgesia system, was compared with alfentanil alone given by the same route for analgesic effect, side effects and acute phase reaction over a 4-day period following anterior cruciate ligament reconstruction of the knee. The patients receiving piroxicam had lower pain scores and consumed less alfentanil. There were no differences with regard to side effects between the two treatment groups, apart from significantly more sedation at 08.00 h on the first postoperative day in the non-piroxicam group. Piroxicam did not influence either the levels of interleukin-6 or the acute phase response to surgery.
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PMID:Systemic piroxicam as an adjunct to patient-controlled analgesia with alfentanil for postoperative pain relief. 875 59

We wanted to evaluate pain relief and endocrine/immune response after local administration of morphine into an abdominal wound. In a randomised double blind design 29 patients undergoing hysterectomy received two blinded injections of morphine and saline. Before surgery the patients in the control group (n = 15) got 10 mg of subcutaneous morphine into an arm and at skin incision 30 ml of saline was infiltrated directly into the wound. The patients in the wound group (n = 14) received 1 ml of saline into an arm before surgery and 10 mg of morphine in 30 ml of saline into the wound at skin incision. Patient controlled analgesia (PCA) with i.v. morphine was used after surgery. Repeated blood samples were obtained from the day before the surgery until 3 days later and analysed for cortisol and interleukin-6 (IL-6). There were no differences between the groups either in pain relief or in the consumption of PCA morphine. The wound group used 47 +/- 15 mg of i.v. morphine and the control group used 50 +/- 16 mg. Peak values for IL-6 and cortisol appeared at 4 h. The area under the curve (AUC) of cortisol at 0-6, 0-10 and 0-20 h was significantly lower in the control group than in the wound group (P < 0.05). High doses of i.v. morphine reduced cortisol and IL-6 levels in the early hours after surgery. The injection of morphine into the wound did not improve pain relief or reduce the consumption of i.v. morphine after surgery. The endocrine stress response to trauma was modified by preoperative administration of morphine.
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PMID:Infiltration of morphine into an abnormal wound; effects on pain relief and endocrine/immune response. 946 25

The peri-operative cytokine response was studied in 13 infants and young children undergoing major surgery. All children were anaesthetized with a combined general and epidural anaesthetic technique, followed by post-operative epidural analgesia with bupivacaine and fentanyl. Blood samples were taken before and after surgery, 24 h post-operatively, and finally, when the children were mobilized and had regained gastrointestinal function. Plasma samples were analysed for tumour necrosis factor-alpha, interleukin-1 alpha, interleukin-1 beta, interleukin-6, interferon-gamma, interleukin-10 and the interleukin-1 receptor antagonist. The cytokine responses were highly variable. Overall, no significant changes between pre- and post-operative plasma concentrations were found. Tumour necrosis factor-alpha and the interleukin-1 receptor antagonist were detectable in all children, and a trend towards an early increase in the interleukin-1 receptor antagonist levels at the end of surgery was seen. The other cytokines were only detectable at low concentrations among a minority of children. In conclusion, this study showed highly variable peri-operative cytokine responses in infants and young children undergoing major surgery.
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PMID:The peri-operative cytokine response in infants and young children following major surgery. 952 42

Neuropeptide Y (NPY) and endogenous opioids (EOPs) such as methionine-enkephalin (Met-enk) regulate similar physiological responses, but it is not known whether nociceptive and immune responses also show analogy after intracerebroventricular (i.c.v.) application. Dose-response studies show that Met-enk stimulates the blood granulocyte and splenic natural killer (NK) cell function of Lewis rats at a low dose (10(2) ng/kg, i.c.v.), whereas a high dose (10(5) ng/kg) causes suppression of innate immune functions associated with analgesia in the hot-plate test. At 15 min, 1 h and 24 h after i.c.v. application, both Met-enk (10(2) ng/kg) and NPY (1 ng/kg) produced similar effects: An initial suppression of innate immune function was followed by a long lasting stimulatory action on cell functions and serum interleukin-6 (sIL-6) levels. Thus, central NPY application resembles Met-enk-induced immunostimulation at doses not affecting nociception, suggesting an involvement of both peptides in shaping stress-induced immunomodulation of the non-analgetic form, possibly via activation of a common immunomodulatory effector mechanism.
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PMID:Centrally applied NPY mimics immunoactivation induced by non-analgesic doses of met-enkephalin. 987 22

Interleukin-6 (IL-6) plays a major role in hematopoiesis, immune functioning, and the acute phase response. In umbilical cord blood, this cytokine was thought to be a marker of neonatal defense to stress and infection, however, neonatal IL-6 production is immature. We speculated that a maternal influence exists on neonatal IL-6, at least during uncomplicated deliveries. Of the 81 healthy parturients included in this study, 51 delivered vaginally, 20 with and 31 without epidural analgesia, and 30 underwent elective cesarean section, 20 with epidural and 10 with general anesthesia. Maternal blood was sampled on hospital admission and just after delivery. Neonatal blood was collected from the umbilical cord. A significant positive correlation was found between neonatal cord blood interleukin-6 levels and maternal serum IL-6 levels on admission (r = 0.57, p <0.001) and just after delivery (r = 0.79, p <0.001). This was not influenced by the type of delivery or anesthesia. Neonatal IL-6 levels were weakly negatively correlated with the duration of gestation and with the Apgar score 1 min after birth. A feto-maternal dependency of neonatal IL-6 on maternal serum IL-6 levels implies a priming or modulatory role of the maternal immune system on that of the neonate.
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PMID:The fetomaternal dependency of cord blood interleukin-6. 1043 93

It has been suggested that the incidence of early graft occlusion after arterial reconstructive surgery to the leg may be decreased by epidural analgesia. This effect may be mediated by the suppression of the usual cortisol response to surgery, which results in increased circulating plasminogen activator inhibitor-1 with consequent adverse effects on fibrinolysis. To investigate this and other potential mechanisms, 30 patients undergoing arterial reconstructive surgery to the leg were randomized to receive either general anaesthesia or general anaesthesia plus epidural analgesia. Post-operative analgesia was provided by morphine infusion or epidural analgesia, respectively. Blood samples were collected at 0, 2, 4, 6, 12 and 24 h, and 2, 3 and 5 days and analysed for cortisol, plasminogen activator inhibitor-1 antigen, interleukin-6 and beta thromboglobulin. The incidence of graft-related and systemic complications was recorded for 30 days. Only one patient developed early graft occlusion that required embolectomy and eventually amputation. There were no significant changes from control values in either group of patients in circulating cortisol, plasminogen activator inhibitor-1 and beta thrombogobulin (a marker for platelet degranulation). Interleukin-6 values increased significantly in both groups after 4 h and remained elevated until day 3. There were no significant differences between the groups in any variable measured. We conclude that any effect of epidural analgesia on early graft patency is unlikely to be mediated by fibrinolysis or platetlet degranulation.
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PMID:Epidural analgesia and arterial reconstructive surgery to the leg: effects on fibrinolysis and platelet degranulation. 1157 65

We have previously shown in rats that both intrathecal and systemic analgesia regimens attenuate surgery-induced increases in tumor susceptibility. The current study used indomethacin to assess the role of prostaglandins and inflammation-associated pain in mediating the deleterious effects of surgery on immunity and tumor susceptibility. Male and female Fischer 344 rats were anesthetized with halothane and were either subjected or not to experimental laparotomy, followed by the administration of indomethacin or vehicle. Tumor susceptibility was assessed by the lung retention assay using the syngeneic MADB106 mammary adenocarcinoma cell line, a natural killer (NK)-sensitive tumor that colonizes only in the lungs. Surgery resulted in a 2- to 3.5-fold increase in lung tumor retention, and indomethacin administration significantly reduced this effect in both sexes without affecting unoperated animals. Indomethacin also attenuated the reductions in rearing behavior evident after surgery, suggesting that it relieved abdominal discomfort. Surgery increased interleukin-6 levels and suppressed NK activity per milliliter blood. Indomethacin restored NK activity in both male and female rats but attenuated surgery-induced interleukin-6 increases only in the male rats. These findings further support our previous work implicating pain in mediating the tumor-enhancing effects of surgery and implicate prostaglandins in mediating this effect. If similar relationships occur in humans, controlling postoperative pain and inflammation must become a priority in the management of cancer patients undergoing surgery.
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PMID:Indomethacin attenuates the immunosuppressive and tumor-promoting effects of surgery. 1462 54

Inflammatory pain is counteracted by a number of physiological processes. For example, opioid receptors, which are present on peripheral terminals of sensory neurons, are activated by endogenous opioids, which are released from immune cells migrating to the inflamed tissue. Earlier data demonstrated that interleukin-6 contributes to such inflammation-induced analgesia. In this report, we demonstrated that interleukin-6 strongly induces mu-opioid receptor mRNA in the human neuroblastoma cell line SH SY5Y, whereas delta-opioid receptor mRNA levels are not influenced. The mRNA increase in these cells is followed by an increase in mu-opioid receptor-specific binding. Using transcription factor decoy oligonucleotides, direct evidence was provided that the up-regulation of mu-opioid receptor mRNA in intact cells is dependent on the transcription factors signal transducers and activators of transcription 1 (STAT1) and STAT3, whereas other transcription factors, such as activator protein-1, nuclear factor (NF)-kappaB, or NF-interleukin-6 are not involved. STAT1 and STAT3 bound to a site located at nucleotide -1583 on the promoter of the human mu-opioid receptor gene, as shown by transient transfection experiments, electrophoretic mobility shift assays, and transcription factor decoy oligonucleotides. A mutation analysis of the 5'-TTCATGGAA-3' STAT1/3 element (palindrome underlined) was performed to determine nucleotide residues that are necessary for the binding of STAT1 and STAT3. It suggested that only the palindromic half sides and the two adjacent central nucleotides are required. Neither mutation of the nucleotides outside the palindrome nor mutation of the central nucleotide affected STAT1/3 binding.
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PMID:Transcriptional regulation of the human mu-opioid receptor gene by interleukin-6. 1544 91


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