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)

Cytosolic aminopeptidase P was obtained in highly purified form from human leukocytes by a four-step procedure. Buffy coats were the starting material. A M(r) of 140,000 was obtained by size-exclusion HPLC for the native enzyme. As shown by SDS/PAGE under reducing and denaturing conditions, the enzyme consisted of likely identical subunits with M(r) of 71,000. Purified aminopeptidase P cleaved off, specifically and efficiently, the N-terminal residues from peptides with N-terminal Xaa-Pro sequences. The penultimate proline was not replaceable by hydroxyproline, alanine and glycine in di-, tri- and tetrapeptides. Polyproline was not hydrolyzed. Dipeptides were cleaved (Arg-Pro, Phe-Pro > Trp-Pro > Pro-Pro) although slower than longer peptides. Cleavage was observed of several biologically active peptides; C-terminal fragment (residues 201-206) of C-reactive protein, oxytocin fragment Tyr-Pro-Leu-Gly, morphiceptin, peptide Gly-Pro-Arg-Pro (inhibitor of fibrin polymerization) and kentsin. In addition, cleavage of a protein, interleukin-6, was also demonstrated. Aminopeptidase P was maximally activated by Mn2+, and to a lesser extent by Co2+. The activity was optimal at pH 8. Ni2+, Zn2+ and especially Cd2+ caused marked inhibition. EDTA, 1,10-phenantroline and dithiothreitol were also inhibitory. Carbobenzoxy-phenylalanine, as well as several N-carbobenzoxy-proline-containing peptides, caused partial inhibition. The observed resistance of Gly-Pro, Pro-Gly, Pro-Phe and Pro-Ile to hydrolysis by the purified enzyme strongly indicates absence of known proline-specific dipeptidases in the aminopeptidase-P preparation.
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PMID:Aminopeptidase P from human leukocytes. 144 89

Due to the stress imposed by the process of bone marrow transplantation (BMT), we hypothesized that individuals receiving such a transplant underwent an acute phase response (APR). Circulating levels of C-reactive protein (CRP), haptoglobin (HAP), alpha-1 acid glycoprotein (AAG), ceruloplasmin (CER), zinc (Zn), copper (Cu), interleukin-6 (IL-6), albumin (ALB), and thyroxine-binding prealbumin (TBPA), were measured at baseline (Day -7), Day -4, Day 0 (Transplant Day), Day +2, +7, and weekly until day 28 in 14 adults receiving an autologous bone marrow transplant as Phase 1 treatment for various hematologic or solid tumor malignancies. Ten of 14 recipients survived, 9 of which had a significant increase in CRP (p = 0.012), HAP (p = 0.011), AAG (p = 0.002), and decrease in ALB (p = 0.002) and TBPA (p = 0.004) on Day +7, but not Day 0, after bone marrow reinfusion. These findings document the presence of an APR and suggest that the bone marrow transplant process (post reinfusion) initiates a stress response in the recipient.
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PMID:The acute phase response in autologous bone marrow transplantation. 147 99

Tumor necrosis factor and related cytokines are thought to be implicated in cell-mediated immunity and pathophysiology in malaria, but their mechanism of action has not been ascertained. Tumor necrosis factor has been reported to generate nitric oxide in vitro, so we have measured levels of this molecule and its products in the plasma of mice after they have received an injection of tumor necrosis factor, lymphotoxin, interleukin-1, gamma interferon, or interleukin-6, all of which have been reported to be increased in malaria. Total reactive nitrogen intermediate levels in plasma were assayed spectrophotometrically after exposing plasma to a copper-cadmium-zinc catalyst to convert nitrate to nitrite and then to Griess reagent. Tumor necrosis factor, lymphotoxin, and interleukin-1 all induced reactive nitrogen intermediates in vivo, with interleukin-1 showing the most activity. Tumor necrosis factor was then examined more closely. It induced more reactive nitrogen intermediates in malaria-infected mice than in normal mice, and appreciably more was in the form of nitrate than was in the form of nitrite. NG-methyl-L-arginine inhibited the in vivo generation of reactive nitrogen intermediates by tumor necrosis factor in a dose-dependent manner, implying that these molecules were arginine derived. These results are consistent with the possibility that tumor necrosis factor, lymphotoxin, and interleukin-1 may contribute to host pathology and parasite suppression through generation of nitric oxide.
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PMID:In vivo induction of nitrite and nitrate by tumor necrosis factor, lymphotoxin, and interleukin-1: possible roles in malaria. 150 Jan 82

Stimulation of the immune system results in a series of metabolic changes that are antagonistic toward growth. Monokines, including interleukin-1, tumor necrosis factor, and interleukin-6, are released from cells of the monocyte-macrophage lineage after recognition of immunogens. They appear to mediate homeorhetic response, which alters the partitioning of dietary nutrients away from growth and skeletal muscle accretion in favor of metabolic processes which support the immune response and disease resistance. These alterations include 1) decreased skeletal muscle accretion due to increased rates of protein degradation and decreased protein synthesis; 2) increased basal metabolic rate resulting in increased energy utilization; 3) use of dietary amino acids for gluconeogenesis and as an energy source instead of for muscle protein accretion; 4) synthesis by the liver of acute phase proteins; 5) redistribution of iron, zinc, and copper within the body due to the hepatic synthesis of metallothionein, ferritin, and ceruloplasmin; (6) impaired accretion of cartilage and bone; and 7) release of hormones such as insulin, glucagon, and corticosterone. These monokines also influence the differentiation of cells. Tumor necrosis factor suppresses the differentiation of myoblasts and adipocytes whereas the chicken monokine myelomonocytic growth factor induces the differentiation of granulocytes.
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PMID:Monokines in growth and development. 171 68

We investigated the effect of human recombinant interleukin-6 (IL-6) on body temperature and acute-phase response, including changes in plasma levels of iron, zinc, copper, and fibrinogen and in circulating leukocyte count. The intravenous (IV) injection of IL-6 (2 micrograms/kg) produced a monophasic fever. The intracerebroventricular (ICV) injection of IL-6 produced a dose-dependent fever that developed gradually and remained elevated throughout the 5-h recording period. The IV injection of IL-6 decreased the plasma concentration of iron and zinc and increased the circulating leukocyte count. The ICV injection of IL-6 resulted in similar trace metal and leukocyte changes, and increased plasma levels of fibrinogen. These results show that IL-6 can cause fever when injected IV or ICV and induces some acute-phase responses through its action on peripheral target organs and in the central nervous system.
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PMID:Fever and acute-phase response induced in rabbits by intravenous and intracerebroventricular injection of interleukin-6. 188 59

The addition of copper and zinc salts to human peripheral blood leukocytes cultured in complete medium containing endotoxin and fetal calf serum stimulated tumor necrosis factor (TNF) secretion in a concentration-dependent manner. The secretion of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) was inhibited by copper under the same culture conditions, while zinc stimulated IL-1 beta secretion in a concentration-dependent manner and had no effect on leukocyte IL-6 release. Both copper and zinc induced increases in TNF mRNA (54 and 14%, respectively) when compared to cells cultured in complete medium alone. In serum-free, low endotoxin medium (less than 6 pg/ml), both copper and zinc failed to stimulate either TNF or IL-1 beta secretion. Under the same conditions the addition of lipopolysaccharide (LPS), at concentrations above 0.01 micrograms/ml, induced a concentration-dependent release of both cytokines. When either copper or zinc were combined with 0.01 micrograms/ml LPS, a synergistic stimulation of TNF secretion resulted. IL-1 beta secretion, unlike TNF, was not synergistically stimulated by combining metals and LPS in serum-free medium. Combining copper and zinc with inhibitors of TNF secretion, transforming growth factor beta, prostaglandin E2, and plasma alpha-globulins, resulted in a reduction of the suppressive effects of each of these agents. This study suggests that the trace metals copper and zinc may play important and possibly distinct roles in regulating leukocyte secretion of TNF, IL-1 beta, and IL-6.
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PMID:Differential effects of copper and zinc on human peripheral blood monocyte cytokine secretion. 210 32

The purpose of this study was to support the hypothesis that cytokines such as interleukin-1, tumor necrosis factor and interleukin-6 are released by macrophages or monocytes within 1 to 2 hr of phagocytosis of circulating, gut-derived bacterial lipopolysaccharide translocated by acute liver injury. Time courses of fever, neutrophilia and low blood-zinc levels generally attributed to cytokines were quantified after partial (67%) hepatectomy of rats under ether anesthesia. These acute phase responses in hepatectomized rats were compared with those after intravenous injection of exogenous endotoxin and human natural interleukin-1. Fever commenced 30 min after interleukin-1 injection, 4 hr after exogenous lipopolysaccharide injection and 6 hr after 67% liver resection. Similarly, rectal temperatures were significantly elevated in recipient rats 30 min after intravenous administration of donor plasma from hepatectomized animals, indicating that cytokines, not lipopolysaccharide, elicited the febrile response. Neutrophilia was present 1, 2, and 4 hr after interleukin-1 injection, lipopolysaccharide injection and hepatectomy, respectively. Furthermore, the reduction in plasma zinc, which depends on cellular metallothionein synthesis, occurred 4 hr after interleukin-1 administration and 6 hr after lipopolysaccharide injection or partial hepatectomy. Donor plasma from hepatectomized rats also elicited neutrophilia at 1 hr and low blood-zinc levels 4 hr after injection in recipient animals. The timing of these responses, just as for the fever, implies that cytokines and not lipopolysaccharide in the donated plasma elicited the neutrophilia and hypozincemia. Evidence was reviewed that interleukin-1, tumor necrosis factor and interleukin-6 function as hepatotrophic factors and have been identified in the circulation of humans with liver damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute phase responses after acute liver injury by partial hepatectomy in rats as indicators of cytokine release. 211 49

Immune responses result in a variety of metabolic adjustments that are mediated by cytokines of leukocytic origin. Of the dozens of cytokines released during an immune response, interleukin-1 (IL-1), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) are the major mediators of intermediary metabolism. These three cytokines act in concert to decrease food intake, increase resting energy expenditure, gluconeogenesis, glucose oxidation, and hepatic synthesis of fatty acids and acute phase proteins, decrease fatty acid uptake by adipocytes and alter the distribution of zinc, iron and copper. Most of these activities result from direct interactions between the cytokine and the responding cells. IL-1, TNF alpha and IL-6 also affect changes in metabolism by changing levels of circulating insulin, glucagon and corticosterone. The nutritional impact of these metabolic changes is dependent upon age. In growing animals, increases in energy expenditure and oxidation of amino acids are balanced by lower needs associated with growth. In adult animals, energy and amino acid requirements are increased by an amount similar to the increased basal metabolic rate and amino acid oxidation. Nutrition also influences the release of cytokines and consequently affects regulation of the immune response. For example, protein deficiency results in decreased IL-1 release and impaired tissue responses to IL-1.
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PMID:Nutritional aspects of leukocytic cytokines. 306 44

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

We have investigated the effect of transforming growth factor-beta 1 (TGF-beta 1) and three cytokines on expression of antioxidative enzymes, manganese-superoxide dismutase, copper, zinc-superoxide dismutase, and catalase in cultured hepatocytes of rat. While interleukin-1 beta and interleukin-6 induced manganese-superoxide dismutase gene expression, they slightly suppressed catalase gene expression in rat hepatocytes. TGF-beta 1 suppressed expression of all these antioxidative enzymes in time- and cell density-dependent manners. Furthermore, we examined the effect of TGF-beta 1 on expression of glutathione peroxidase and glutathione-S-transferase, which exhibit glutathione-dependent peroxidase activity in rat hepatocytes. Expression of two major classes of the rat glutathione-S-transferase subunits 1 and 2 was also reduced by TGF-beta 1, although expression of glutathione peroxidase was not affected. Flow cytometric analysis indicated that production of peroxides was increased in hepatocytes treated with TGF-beta 1. These data suggest that augmented production of hydrogen peroxide and its intermediate through suppression of antioxidative enzyme expression may participate in cellular injury or growth inhibition promoted by TGF-beta 1.
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PMID:Suppression of antioxidative enzyme expression by transforming growth factor-beta 1 in rat hepatocytes. 751 58


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