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)

In an uncontrolled clinical trial the effects of repeated administration of the F(ab')2 fragment of a murine monoclonal anti-tumor necrosis factor alpha (TNF alpha)-antibody (MAK 195F) on cytokine levels and the cardiovascular system were studied in 20 patients with severe sepsis. Patients were treated with a total of 11 single dosages of the anti-TNF alpha-antibody intravenously over 5 days using either 1 mg/kg (n = 10) or 3 mg/kg (n = 10). The anti-TNF alpha-antibody was well tolerated in all patients without signs of toxicity and without development of anti-murine antibodies. As assessed by cytokine levels (TNF alpha, Interleukin-6) and hemodynamics there was no evidence that the higher dosage of the anti-TNF alpha-antibody (3 mg/kg per dose) was more effective than the lower dosage (1 mg/kg per dose). Comparison of our data with recent data from phase I or II trials using a complete murine monoclonal anti-TNF alpha-antibody suggest that the F(ab')2 fragments of the murine monoclonal anti-TNF alpha-antibody may be of similar efficacy. Definitive conclusions, however, with respect to improvement of mortality and improvement of the cardiovascular system, await the results of larger ongoing placebo-controlled trials.
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PMID:Repeated administration of a F(ab')2 fragment of an anti-tumor necrosis factor alpha monoclonal antibody in patients with severe sepsis: effects on the cardiovascular system and cytokine levels. 773 57

Endotoxin is a potent activator of the complement system and other host immunoregulators, including the cytokines, tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6. In this study, the potency of an endotoxin from bicarbonate dialysate was compared with endotoxins from two enteric microorganisms, Shigella flexneri and Escherichia coli. Endotoxin concentrations were standardized for the three endotoxins by use of the Limulus amebocyte lysate turbidimetric assay. Endotoxin potency was assessed by the comparative plasma concentrations of tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 after an in vitro whole-blood challenge by each type of endotoxin. Blood collected from 10 hemodialysis patients was spiked with 0.1, 1, and 10 ng/mL of E. coli and Shigella endotoxin and with 1 and 10 ng/mL of bicarbonate dialysate endotoxin. After incubation, plasma was separated and frozen at -70 degrees C until assayed for cytokine concentrations. Dialysate endotoxin was found to be 10 to 100 times less potent than E. coli and Shigella endotoxins. It was concluded that there are significant differences in the potency of endotoxins from different strains of bacteria and that these differences should be noted when designing or evaluating studies on the clinical effects of endotoxins in hemodialysis settings.
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PMID:Potency of endotoxin from bicarbonate dialysate compared with endotoxins from Escherichia coli and Shigella flexneri. 775 98

This study investigated the effects of feeding mice lipids with different fatty acid compositions upon the ability of stimulated macrophages to produce inflammatory mediators. Weanling mice were fed for 8 weeks on a low-fat (LF; 2.5% by weight) diet or on diets containing 20% by weight of hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO), or menhaden (fish) oil (MO). Thioglycollate-elicited peritoneal macrophages were isolated. Macrophages isolated from MO-fed mice produced less PGE2, 6-keto-PGF1 alpha, TXB2, and interleukin-6 in response to lipopolysaccharide (LPS) stimulation than those from mice fed each of the other diets. Macrophages from mice fed the OO, SO, or MO diets produced less tumor necrosis factor alpha in response to LPS stimulation than those from mice fed the LF or HCO diets. There was no effect of dietary lipid manipulation upon the production of interleukin-1 by LPS-stimulated macrophages. Macrophages from mice fed the MO diet produced more superoxide and hydrogen peroxide in response to phorbol ester stimulation than those from mice fed each of the other diets. In response to unopsonized zymosan, macrophages from mice fed the SO or MO diets produced more hydrogen peroxide than macrophages from mice fed the other diets. LPS-stimulated nitric oxide production was greater from macrophages from OO-, SO-, or MO-fed mice than from those fed the LF or HCO diets. Thus, the nature of the lipid consumed in the diet has significant effects upon the production of a variety of inflammatory mediators by macrophages. The most potent effect is caused by fish oil consumption. Possible mechanisms by which dietary fatty acids, particularly the n-3 polyunsaturated fatty acids found in fish oils, could affect mediator production by macrophages are described. The clinical relevance of such effects is discussed.
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PMID:Effects of dietary lipid manipulation upon inflammatory mediator production by murine macrophages. 775 22

The concentration and accessibility of endotoxin can increase following antibiotic killing of gram-negative bacteria. There are indications that antibiotics may differ in this respect. We measured endotoxin levels in RPMI 1640 and tumor necrosis factor alpha (TNF-alpha) and interleukin-6 production in whole blood ex vivo after exposure of log-phase Escherichia coli to antibiotics belonging to different classes, in a final concentration of 0.5, 5, or 50 times the MIC. After 4 h of incubation at 50 times the MIC, ceftazidime and ciprofloxacin treatment resulted in levels of endotoxin, TNF-alpha, and interleukin-6 significantly higher than those of imipenem and gentamicin (P < 0.001). Similar differences in cytokine induction were measured after 8 h of incubation. At 0.5 times the MIC, the differences between the antibiotics in measured endotoxin and cytokine levels were small, with levels comparable to the levels in untreated cultures. Polymyxin B and, to a lesser degree, recombinant bactericidal/permeability-increasing protein 21 (rBPI-21) were found to be potent inhibitors of TNF-alpha release, supporting the concept that the differences between the antibiotics in cytokine production were indeed due to differences in amounts of biologically active endotoxin. The presence of serum from patients suffering from untreated sepsis decreased TNF-alpha production significantly, in a concentration-dependent manner.
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PMID:Release of tumor necrosis factor alpha and interleukin 6 during antibiotic killing of Escherichia coli in whole blood: influence of antibiotic class, antibiotic concentration, and presence of septic serum. 776 3

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.
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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

Levels of cytokines released from endotoxin-mediated monocytes were investigated in mice of DBA/2, BALB/c, C57BL/6, C3H/He, ddY and ICR strains and in ICR mice of various ages (4-52 weeks old). Interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) levels from monocytes were low in DBA/2 and BALB/c mice, and high in ddY and ICR strains. In addition, interleukin-6 (IL-6) levels were low in DBA/2, and high in ddY and ICR strains. Therefore, monocytes obtained from ddY and ICR strain mice released large amounts of cytokines as compared to those from the DBA/2 strain. The levels of IL-1 alpha, IL-1 beta and IL-6 released from monocytes of ICR mice were constant at 4-18 weeks old, and low at 26 and 52 weeks old. In contrast, the TNF alpha level was low at 18 weeks and high at 26 and 52 weeks. These results indicate that age-associated changes in cytokine release from monocytes correlate well with the cytokine levels in bone marrow.
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PMID:[Strain- and age-associated changes in cytokine release from endotoxin-treated mouse monocytes]. 780 99

Comparison was made between the immunobiological and antigenic properties of two lipoteichoic acid (LTA) fractions (LTA-1 and -2) from Enterococcus hirae ATCC 9790, their glycolipid portions, and synthetic compounds partially mimicking the above bacterial products. The more lipophilic LTA-2 fraction was capable of inducing serum tumor necrosis factor alpha and interleukin-6 in muramyldipeptide-primed mice and serum gamma interferon in those primed with Propionibacterium acnes. The LTA-2 fraction also induced tumor necrosis factor alpha, interleukin-6, and thymocyte-activating factor (essentially interleukin-1) in murine peritoneal macrophage cultures. Consecutive intravenous injections of muramyldipeptide and the LTA-2 fraction in Meth A fibrosarcoma-bearing BALB/c mice caused hemorrhagic necrosis and marked regression leading to complete regression of the tumor with no accompanying weakening or lethal effects. The LTA-2 fraction was at least 10,000-fold less pyrogenic in rabbits than a reference endotoxic lipopolysaccharide. The more hydrophilic LTA-1 fraction, on the other hand, showed at most marginal activity in the in vivo and in vitro assays. Natural glycolipids (NGL-1 and -2) which were prepared from a chloroform-methanol extract of Streptococcus pyogenes and E. hirae cells, and comparable in structure to the lipid moieties of the LTA-1 and -2 fractions, respectively, were practically inactive in all of the assays. None of the test synthetic compounds was immunobiologically active, although synthetic partial counterparts of the structure of LTA proposed by W. Fischer (Handb. Lipid Res. 6:123-234, 1990) reacted with murine monoclonal antibody TS-2, which was raised against OK-432, a penicillin-killed S. pyogenes preparation, and capable of neutralizing the cytokine-inducing activities of the LTA-2 fraction.
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PMID:Molecular and structural requirements of a lipoteichoic acid from Enterococcus hirae ATCC 9790 for cytokine-inducing, antitumor, and antigenic activities. 780 84

Marked differences in the abilities of living and heat-killed Brucella abortus and Listeria monocytogenes organisms to induce production of tumor necrosis factor alpha by in vitro-cultured macrophages were observed. Interleukin-1 and interleukin-6 appeared to be under different control. The results are discussed in relation to the induction of gamma interferon-producing Th1 cells and acquired cellular resistance to infection by living vaccines but not killed vaccines.
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PMID:Differential induction of macrophage-derived cytokines by live and dead intracellular bacteria in vitro. 782 49

The 27E10 antigen is a heterodimer of MRP8 and MRP14, two Ca(2+)-binding proteins related to the S-100 protein family. Previous studies have shown that 27E10 epitope-bearing monocyte subsets are prevalent in early acute but absent in chronic inflammatory conditions. These observations further provide an impetus for identifying the cellular mechanisms responsible for the appearance of different monocyte subpopulations during inflammation. Therefore this in vitro study was carried out to investigate the influence of adhesion in inducing 27E10-positive subsets. In adhesion assays the role of 27E10 antigen in spontaneous adherence was obvious, as a monoclonal antibody directed against the 27E10 antigen significantly inhibited the adherence of monocytes to collagen and fibronectin. In contrast, these extracellular matrix (ECM) proteins induce the cell surface expression and association of 27E10 antigen with cytoskeleton (CSK), detected by flow cytometry and confocal laser scan microscopy, respectively. Similar results were obtained on cross-linking with specific antibodies, thus showing involvement of the integrin molecules VLA-2 and VLA-4. In addition, the association with CSK could be confirmed by differential detergent extraction. The observed redistribution of 27E10 antigen guided by collagen compared with fibronectin was also paralleled by an augmented release of inflammatory cytokines interleukin-6, tumor necrosis factor alpha, and superoxide anions. Thus, this study demonstrates that under inflammatory conditions the interactions of extravasating monocytes with the ECM may induce an activated phenotype of monocytes marked by 27E10.
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PMID:Heterodimers of the calcium-binding proteins MRP8 and MRP14 are expressed on the surface of human monocytes upon adherence to fibronectin and collagen. Relation to TNF-alpha, IL-6, and superoxide production. 782 73

The clinical syndrome of cachexia is characterized by anorexia, continued losses of lean body mass, and altered carbohydrate and lipid metabolism. As early as the 1930s, this "chronic wasting" syndrome had been identified as the most frequent immediate cause of death in patients with cancer [Warren: Am J Med Sci 184:610-619, 1932]. At present, controversy remains as to the benefit of supplemental parenteral or enteral feedings in the nutritional repletion of cachectic cancer patients, since only selected patient groups have demonstrated clear benefit from their administration [Copeland et al.: Cancer 43:2108-2116, 1979; Copeland et al.: Cancer Res 37:2451-2456, 1977; Terepka and Waterhouse: Am J Med 20:225-238, 1956]. Despite having these advanced nutritional modalities firmly in our therapeutic armamentarium, the progression of cachexia in the nutritionally depleted cancer patient often continues unabated, and our ability to intervene successfully remains limited. This review proposes that host: tumor interactions lead to a nonspecific inflammatory response mediated in part by the chronic production and release of proinflammatory cytokines, including interleukin-1, tumor necrosis factor alpha, interleukin-6 and interferon-gamma, which antagonize the anabolic signals associated with enteral and parenteral nutrition support. Cytokine-mediated alterations can explain the inability of adequate dietary nitrogen and calories to result in lean tissue repletion. Based on this proposal, interrupting proinflammatory cytokine production or target organ action may be an appropriate therapeutic objective to improve nutrient utilization in patients with tumors.
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PMID:Cytokine-mediated alterations in host metabolism prevent nutritional repletion in cachectic cancer patients. 784 87


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