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

The influence of peplomycin (PLM) and azelastine hydrochloride (Azeptin) on reactive oxygen (RO) and cytokine generation was examined in human peripheral blood mononuclear leukocytes, polymorphonuclear leukocytes (PMN), and rabbit alveolar macrophages (RAM). In addition, the influence of these drugs on DNA and collagen synthesis was investigated in human gingival and rabbit pulmonary fibroblasts. In vitro, PLM increased the FMLP- and PMA-induced chemiluminescence and superoxide (O2-) generation in human PMN and RAM in a dose-dependent manner. In contrast to PLM, Azeptin dose-dependently suppressed RO generation. Such contrasting actions of PLM and Azeptin were also observed in RAM and PMN obtained from rabbits treated with PLM or Azeptin. Even when human PMN were preincubated with 10-100 micrograms/ml of PLM, the increase in RO generation was negligible in the presence of 10(-5) M Azeptin in the culture medium. No increases in RO generation were observed in RAM or PMN obtained from rabbits that had received PLM (0.1 mg/kg per day) and Azeptin (0.04 mg/kg per day) concomitantly. PLM suppressed superoxide dismutase activity in RAM and human PMN, while Azeptin did not affect this activity. In vitro, PLM up-regulated the release of interleukin-1 beta, interleukin-6, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor both from human cells and from RAM and pulmonary fibroblasts. In the generation of these cytokines, Azeptin abrogated the up-regulatory action of PLM. PLM and Azeptin also had contrasting actions in [3H]thymidine and [3H]proline incorporation in human and rabbit fibroblasts. Furthermore, protein tyrosine phosphorylation, in particular that of a 115-kDa protein in human PMN, was suppressed by Azeptin and enhanced by PLM. These results seem to indicate that up-regulated RO and collagen generation are the causative factors of PLM-induced pulmonary fibrosis and that Azeptin may suppress the adverse effect.
 ...
PMID:Contrasting influence of peplomycin and azelastine hydrochloride (Azeptin) on reactive oxygen generation in polymorphonuclear leukocytes, cytokine generation in lymphocytes, and collagen synthesis in fibroblasts. 780 82

Mycoplasmas and mycoplasma membranes have been shown to induce the production of inflammatory cytokines, including tumor necrosis factor alpha and interleukin-6, as well as nitric oxide, by mouse macrophages and rat brain astrocytes. Luminol-enhanced chemiluminescence was used as a sensitive method to show that Mycoplasma capricolum membranes induce mouse peritoneal macrophages to produce reactive oxygen radicals. Coincubation of the mycoplasma with a secondary stimulus, namely macrophage-activating factor or interferon-gamma, increased the chemiluminescence. The augmentation was abolished by the nitric oxide synthase inhibitor NG-methyl-L-arginine, indicating the involvement of nitric oxide. The coproduction of superoxide and nitric oxide by the same cell allows the formation of the powerful oxidant peroxynitrite, which could be responsible for the increased chemiluminescence. Induction of oxidizing radicals by mycoplasmas may contribute to the clinical pathology seen in mycoplasma infections.
 ...
PMID:Mycoplasma stimulates the production of oxidative radicals by murine peritoneal macrophages. 785 40

Serum levels of interleukin-6, interleukin-8, the soluble receptor for tumor necrosis factor (sTNFr), and the soluble receptor for intercellular adhesion molecule-1 (sICAM-1) were measured serially in a series of 13 severely injured trauma patients to determine if any of these elements of the inflammatory response are predictive of multiple organ failure (MOF). Six of the 13 patients developed MOF as determined by a MOF scoring system. At the completion of resuscitation (when oxygen delivery and consumption were maximized) sICAM-1 levels were significantly higher in MOF patients before the development of clinical evidence of organ failure (700 +/- 67 ng/mL) compared with non-MOF patients (302 +/- 18 ng/mL). There was a significant correlation between the absolute level of sICAM-1 at the time of resuscitation and the severity of subsequent MOF. This finding suggests that leukocyte-endothelial cell interactions are upregulated immediately after injury and may be implicated in the end-organ injury that leads to MOF.
 ...
PMID:Elevated levels of soluble ICAM-1 correlate with the development of multiple organ failure in severely injured trauma patients. 791 40

Redox-based modulation plays a role in transcriptional control of gene expression. In the present study, we investigated the possible role of reactive oxygen species in the induction of interleukin-6 (IL-6) mRNA and in increases in NF kappa B binding activity by tumor necrosis factor (TNF) alpha using a mouse fibroblastic cell line, Balb/3T3. Expression of IL-6 mRNA is known to be dependent upon NF kappa B that binds to the 5'-flanking region of the IL-6 gene. We found that: (i) TNF alpha increased IL-6 mRNA levels and this increase was inhibited by N-acetyl-L-cysteine (NAC), a scavenger of reactive oxygen species. (ii) NF kappa B binding activity in this cell line was also increased by TNF alpha, and the increase was inhibited in the presence of NAC. (iii) The treatment of cells with low doses of hydrogen peroxide increased the NF kappa B binding activity. (iv) Expression of a reporter gene in which the chloramphenicol acetyltransferase (CAT) gene was under the control of NF kappa B binding sites was induced by hydrogen peroxide. These results suggest that the induction of IL-6 mRNA is regulated by a mechanism involving reactive oxygen species and that NF kappa B, whose activity is sensitive to the cellular redox state, plays an important role in this induction in a fibroblastic cell line, Balb/3T3, stimulated with TNF alpha.
 ...
PMID:Inhibition by N-acetyl-L-cysteine of interleukin-6 mRNA induction and activation of NF kappa B by tumor necrosis factor alpha in a mouse fibroblastic cell line, Balb/3T3. 792 24

Patients requiring mechanical ventilation can develop severe pulmonary injury. Although pentoxifylline (PTX) is known to attenuate endotoxin and tumor necrosis factor (TNF)-induced lung injury, as well as decrease interleukin-6 (IL-6) levels following hemorrhage and resuscitation, it remains unknown if this agent has any beneficial effects against O2-induced lung injury. The aim of this study, therefore, was to determine if PTX attenuates pulmonary oxygen toxicity. To investigate this, male Sprague-Dawley rats were injected subcutaneously with 1 ml saline or 1 ml PTX (50 mg/kg) and immediately exposed to either 21% O2 or > or = 95% O2 for 52 hr. The animals were then reweighed and euthanized. Pleural fluid was collected, blood samples were obtained, and lung lavage was performed. Lactate dehydrogenase (LDH) activity, protein content, and IL-6 concentrations were determined in the lavage fluid and serum. The supernatant LDH activity, protein content, pleural fluid accumulation, and IL-6 concentration were significantly decreased (P < 0.05) in those animals pretreated with PTX prior to exposure to hyperoxia compared to those animals exposed to hyperoxia and not treated. Furthermore, the hematocrit and serum IL-6 concentration were also decreased in the treated group and not significantly different from the controls. Thus, PTX appears to attenuate O2-induced lung injury and may play a role in protecting those patients at risk for developing pulmonary oxygen toxicity.
 ...
PMID:Pentoxifylline attenuates oxygen-induced lung injury. 801 9

Ascites is a readily available source of human macrophages (M phi), which can be used to study M phi functions in vitro. We characterized the mediators of inflammation produced by human peritoneal M phi (hp-M phi) obtained from patients with portal hypertension and ascites. The production of the cytokines interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) was found to be lipopolysaccharide (LPS) concentration dependent (0-10 micrograms/ml) with a maximal production at 10 micrograms/ml and also dependent on the time of exposure to the stimulus (0-36 h). IL-1 beta, IL-6 and TNF-alpha production after LPS administration reached a plateau at 24 h. In vitro stimulation for 24 h with LPS does not influence the eicosanoid production from endogenous arachidonate. 13 min of exposure of the cells to the calcium ionophore A23187 gives a significant increase in eicosanoid production from both exogenous and endogenous arachidonate. The main eicosanoids produced are the 5-lipoxgenase products LTB4 and 5-hydroxyeicosatetraenoic acid (HETE). The increase in production of the other eicosanoids is not significant. The eicosanoid production depends on the stimulus concentration. The optimal A23187 concentration is 1 microM. Oxygen radical production was measured in the M phi by a flowcytometric method. The fluorescence intensity of phorbol 12-myristate 13-acetate stimulated and dihydro-rhodamine 123 loaded hp-M phi increases significantly after 15 min. We conclude that LPS stimulation of hp-M phi from liver disease results in similar production of IL-1 beta, IL-6 and TNF-alpha, but that the profile of the eicosanoid production of these M phi stimulated with LPS and A23187 differs from M phi of other origin and species.
 ...
PMID:Production of inflammatory mediators by human macrophages obtained from ascites. 802 53

The influence of OK-432, a streptococcal preparation, on human polymorphonuclear leukocytes (PMN) was examined. OK-432 increased O2- generation was also observed when PMN were cultured with 10(-2)KE/ml OK-432 for 1 h and then stimulated with phorbol myristate acetate or formyl-metionyl-leucil-phenylalanine (FMLP). In addition, PMN O2- generation was promoted by culture supernatants of peripheral blood mononuclear cells (PBMC) incubated with 10(-3) or 10(-2) KE/ml OK-432. Furthermore, OK-432 (10(-3)-10(-2) KE/ml) enhanced the chemiluminescence of FMLP- and PMA-stimulated PMN. However, nitroblue tetrazolium reduction and myeloperoxidase activity were only minimally enhanced. Not only the candidacidal activity of PMN but also antibody-dependent cell-mediated cytotoxicity against Candida and Raji cells were enhanced in correspondence with the increased generation of reactive oxygen species. Culture of PMN or PBMC for 24 h with OK-432 resulted in a concentration-dependent increase in the substantial production of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha. OK-432 also enhanced granulocyte-macrophage colony stimulating factor and gamma-interferon generation by leukocytes in a dose-dependent manner. Our research indicates that OK-432 enhances PMN function directly as well as via the promotion of cytokine production, and suggests that these effects of OK-432 could be beneficial in immunosuppressed patients.
 ...
PMID:Enhancement of polymorphonuclear leukocyte (PMN) function by OK-432. 815 May 58

Minimal invasive, or more specifically laparoscopic surgery is now the standard procedure in an increasing number of surgical specialties. Inflating the abdomen with CO2 for long periods confronts the anesthesiologist with a number of problems that influence the choice of anesthetic and the monitoring deemed necessary. The increased intraabdominal pressure (IAP) and for some operations the extreme Trendelenburg position can disturb alveolar ventilation and compromise oxygenation. Pulse oximetry is therefore required to recognize and counteract these effects. The insufflated CO2 is absorbed into the blood to an unpredictable extent, and must be eliminated via the lungs by increasing the minute ventilation. Only capnometry or serial blood gas analyses can provide the information needed to correctly adjust the respiration. The endocrine stress reactions to laparoscopic surgery do not appear to be less pronounced than after conventional operations; only the interleukin-6 response to laparoscopic cholecystectomy is reduced compared to the subcostal incision. But minimal invasive surgery offers an advantage at least for cholecystectomy in that there is less impairment of postoperative respiratory function. General anesthesia will be the method of choice for laparoscopic surgery in all but a few procedures in which regional anesthesia is an acceptable alternative. Balanced anesthesia or total intravenous anesthesia is to be preferred, and the drugs employed should have rapid elimination kinetics with a short recovery time, since wound closure time is drastically reduced. Inhalational anesthesia alone may inhibit hypoxic pulmonary vasoconstriction thereby unduly increasing oxygen desaturation. The necessary degree of muscle relaxation still remains to be defined.
 ...
PMID:[Anesthesiologic aspects of minimally invasive surgery]. 825 24

1. This study examined the influence of H2O2, interleukin-6 and platelet-derived growth factor on the proliferation of rat mesangial cells. Mesangial cells were exposed to either a single pulse or three daily pulses of H2O2 (10(-8)-10(-4) mol/l), alone or in combination with interleukin-6 (5 ng/ml) and/or platelet-derived growth factor (10 ng/ml). Proliferation was assessed after 24 h and 72 h of incubation using [3H]thymidine incorporation and cell counts. 2. Although one pulse of H2O2 had no significant effect on mesangial cell proliferation, three daily pulses of 10(-6) mol/l H2O2 resulted in a significant increase in [3H]thymidine incorporation of 31 (52.6, 10.3)% (median and 75th-25th interquartile range) (P < 0.001). Both interleukin-6 and platelet-derived growth factor were also mitogenic to mesangial cells, [3H]thymidine incorporation increasing by 19 (36.7, -6.7)% (P < 0.05) and 53.5 (107, 21.9)% (P < 0.001), respectively. The mitogenic effect of interleukin-6 was enhanced by 10(-6) mol/l H2O2 [49.9 (77.7, 12.3)%] (P < 0.01), whereas the addition of 10(-6) mol/l H2O2 to platelet-derived growth factor resulted in a summated increase in [3H]thymidine incorporation of 82.7 (113, 57.4)% (P < 0.001). Incubation with all three substances simultaneously resulted in down-regulation of growth compared with H2O2 plus platelet-derived growth factor by 55.4 (77.7, 10.3)% (P < 0.05). 3. These findings suggest that reactive oxygen species may play a major role in determining the mesangial cell proliferation that occurs in certain forms of glomerulonephritis, acting either alone or in combination with other growth factors.
 ...
PMID:Interactions of hydrogen peroxide with interleukin-6 and platelet-derived growth factor in determining mesangial cell growth: effect of repeated oxidant stress. 828 68

We examined the effects of surgical trauma on polymorphonuclear leukocyte (PMN) chemotaxis, production of phagocytosis-dependent intracellular chemiluminescence (CL) and production of phagocytosis-independent total CL in two groups: group A with esophageal cancer, and group B with gastric cancer. The scale of surgical trauma was quantified by measuring interleukin-6 in plasma and exudate from drainage tubes. We found a significant augmentation of chemotaxis, total CL and intracellular CL in both groups during the post-operative week. In group A, the increments in both chemotaxis and total CL of circulating cells were smaller than those in group B, but there was no significant difference in intracellular CL between the two groups. Exudate PMNs were more chemotactic, but produced smaller amounts of total CL than circulating cells. No significant difference in intracellular CL between exudate and circulating PMNs was detected, indicating that phagocytic activity was not affected. We conclude that severe surgical trauma causes circulating PMNs with high chemotactic activity to migrate to sites of injury, but that preactivated PMNs in exudate examined in vitro produce lower amounts of reactive oxygen metabolites in response to soluble chemoattractants in vitro than cells circulating in plasma.
 ...
PMID:Differential activation of polymorphonuclear leukocytes from peripheral blood and exudate in surgical patients. 833 Jun 39


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>