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)

Taurine chloramine (TauCl) is produced during inflammation by reaction of hypochlorous acid (HOCl) with taurine, the most abundant free amino acid in neutrophils. We previously reported that TauCl inhibits the generation of macrophage inflammatory mediators such as nitric oxide, prostaglandin E2 (PGE2), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). In this study, the activity of TauCl in modulating T-cell activation was investigated. Treatment of T cells with TauCl (0.1-0.3 mM), prior to activation, was found to inhibit interleukin-2 (IL-2) release in response to both mitogen and antigen stimulation. Similarly, pretreatment of A-20 antigen presenting cells (APCs), at low cell numbers, was found to inhibit their ability to process and present ovalbumin (OVA) to a specific T-cell hybridoma. In contrast, pretreatment of higher numbers of A-20 cells with TauCl in the presence of OVA enhanced subsequent presentation of OVA. Finally, OVA modified with TauCl was processed and presented more efficiently than native OVA. Thus, TauCl is able to modulate induction of a specific adaptive immune response at several independent points of the overall antigen-presenting pathway.
 ...
PMID:Modulation of antigen-specific T-cell activation in vitro by taurine chloramine. 976 13

We previously reported that taurine chloramine (TauCl), a product of activated neutrophils, inhibits the generation of macrophage inflammatory mediators such as nitric oxide (NO), TNF-alpha, and PGE2. Taurine, the most abundant free amino acid in the cytosol of neutrophils, is chlorinated to form TauCl by the halide-dependent myeloperoxidase (MPO) system. Under physiological conditions, TauCl reduces HOCl toxicity. In this study, we investigated the influence of TauCl on generation of oxygen free radicals, cytokines and eicosanoids by activated murine peritoneal neutrophils. We found that TauCl, but not taurine alone, inhibited the production of NO, prostaglandin E2, interleukin-6 and tumor necrosis factor-alpha, in a dose-dependent manner. In contrast, the products of the respiratory burst, as measured by luminol-dependent chemiluminescence (LCL), were reduced by both taurine and TauCl. However, taurine affected LCL at higher concentrations and to a lesser extent than TauCl. The results of these studies suggest that TauCl decreases production of tissue-damaging inflammatory mediators and may regulate the balance between protective, microbicidal and toxic effect of neutrophils.
 ...
PMID:Taurine chloramine down-regulates the generation of murine neutrophil inflammatory mediators. 977 76

Cytokine responses in human host-protective immunity to malaria have yet to be completely elucidated. No data appear to exist on the cytokine patterns in non-human primate models immunized with malarial antigens. Expression of mRNA transcripts of 10 cytokines, the adhesion molecule ICAM-1 and inducible nitric oxide synthase (iNOS) in peripheral-blood mononuclear cells (PBMC) from nine Aotus monkeys was analysed by reverse-transcriptase PCR. Five of the monkeys had been immunized with multiple-antigen peptides (MAP) of the Plasmodium vivax circumsporozoite protein and two with constructs of the P. falciparum merozoite surface protein-1 (MSP-1). The other two monkeys served as non-immunized controls. PBMC were cultured for 24 h after stimulation with phytohaemagglutinin mitogen, MAP and MSP-1 antigens. Elevated expression of interleukin-6 (IL-6), IL-10, IL-12, tumour necrosis factor-alpha (TNF-alpha), TNF-beta and iNOS was seen in response to the MAP. Monkeys immunized with either P. falciparum MSP r190L or synthetic 190L peptides expressed predominantly the type-1 cytokines (IL-1 beta, IL-12, interferon-gamma, TNF-alpha, TNF-beta) characteristic of splenic, cell-mediated activity with macrophage activation and nitric oxide production.
 ...
PMID:Expression of cytokine genes in Aotus monkeys immunized with synthetic and recombinant Plasmodium vivax and P. falciparum antigens. 979 28

It was recently demonstrated that the diffusible messenger molecule nitric oxide (NO) is involved in the febrile response of rats and rabbits to exogenous or endogenous pyrogens. In this study we have investigated the effects of systemic administration of the NO-synthase inhibitor N-nitro-l-arginine-methylester (l-NAME) on abdominal temperature and on lipopolysaccharide- (LPS-) induced fever in guinea-pigs. We further studied the effects of l-NAME on the LPS-induced circulating cytokine network by measurement of tumor necrosis factor alpha (TNF) and interleukin-6 (IL-6) in blood plasma during the time course of fever. At a dose of 10 mg/kg, intra-arterial injection of l-NAME per se had no influence on the abdominal temperature of guinea-pigs, while administration of 50 mg/kg l-NAME evoked a pronounced fall of body temperature which lasted about 12 h. When injected simultaneously with 10 microgram/kg LPS into the arterial circulation, the lower dose of l-NAME that did not decrease abdominal temperature per se caused a significant attenuation of LPS-induced fever due to suppression of the second phase of the biphasic febrile response. The LPS-induced cytokine network remained unimpaired by the treatment with l-NAME. Peak activity of TNF in plasma (measured 60 min after LPS injection) was 20,596+/-2368 pg/ml in control animals and 18,900+/-4778 pg/ml in guinea-pigs treated with l-NAME. In addition, circulating levels of IL-6 were not statistically different between both groups of animals 60 min or 180 min after administration of LPS along with l-NAME or vehicle. The results confirm that endogenous NO formation has a role in the generation of LPS-induced fever and demonstrate that the attenuation of fever by inhibition of NO-synthase is independent of the circulating LPS-induced cytokine network.
 ...
PMID:Inhibition of nitric oxide synthase attenuates lipopolysaccharide-induced fever without reduction of circulating cytokines in guinea-pigs. 979 99

The sympathetic nervous system innervates immune organs and, when activated, releases its signaling molecules in the vicinity of immune cells. The released molecules include the "classical" transmitters norepinephrine and epinephrine and the co-transmitters ATP and adenosine. Immune cells express various adrenergic and purinergic receptors that are sensitive to these molecules, and the production of immune/inflammatory mediators (cytokines, chemokines, and free radicals) is modulated by activation of these receptors. Notably, the production of tumor necrosis factor-alpha, interleukin-6, -10, and -12, and the chemokine macrophage inflammatory protein 1alpha and the production of the free radical nitric oxide, produced by the inducible nitric oxide synthase, have been shown to be altered by activation of these receptors. Alterations in the production of the immune mediators may contribute to the development of various diseases. On the other hand, novel experimental therapies based on the modulation of adrenergic or purinergic receptors on immune cells are emerging. Such approaches may have beneficial effects in limiting tissue injury and suppressing symptoms in certain pathophysiological states.
 ...
PMID:Regulation of cytokine and chemokine production by transmitters and co-transmitters of the autonomic nervous system. 980 16

We have recently observed that the selective adenosine A3 receptor agonist N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) augments interleukin-10 and inhibits tumor necrosis factor-alpha production in endotoxemic mice. In the present study, we extended our investigations into the effect of this compound on the bacterial lipopolysaccharide (endotoxin)-induced inflammatory response in the BALB/c, as well as in the C57BL/6 interleukin-10+/+ and the interleukin-10 deficient C57BL/6 interleukin-10(0)/0 mice strains. In the BALB/c mice, i.p. pre-treatment with IB-MECA (0.2 and 0.5 mg/kg) decreased lipopolysaccharide (60 mg/kg i.p.)-induced plasma levels of interleukin-12 (p40 and p70), interferon-gamma, and nitrite/nitrate (breakdown products of nitric oxide (NO)). On the other hand, pre-treatment with this compound failed to influence lipopolysaccharide-induced plasma interleukin-1 alpha, interleukin-6, and corticosterone concentrations. Similar to its effect in BALB/c mice, IB-MECA enhanced the release of interleukin-10 in the C57BL/6 interleukin-10+/+ mice. Furthermore, IB-MECA inhibited the production of interleukin-12, interferon-gamma, and NO in both the C57BL/6 interleukin-10+/+ and C57BL/6 interleukin-10(0)/0 mice, suggesting that the inhibition of pro-inflammatory cytokine production by this compound is independent of the increased release of interleukin-10. Finally, pre-treatment with this compound protected mice against lipopolysaccharide (60 mg/kg i.p.)-induced lethality. These results indicate that stimulation of adenosine A3 receptors has potent anti-inflammatory effects and may represent a potential strategy in the treatment of septic shock and other inflammatory diseases.
 ...
PMID:An agonist of adenosine A3 receptors decreases interleukin-12 and interferon-gamma production and prevents lethality in endotoxemic mice. 982 93

Lipid A is the active center of bacterial lipopolysaccharide (LPS), which exhibits diverse biological activities via the production of various mediators. We investigated the production of nitric oxide (NO), one of the mediators, by a murine macrophage cell line, RAW264. 7, upon stimulation with a series of monosaccharide lipid A analogues to elucidate the relationship of structure and activity in NO production. The production of other representative mediators, such as tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), was also investigated to compare the structural requirements for the production of these cytokines with those for the production of NO. Structure-activity relationships in NO production correlated well with those in the production of TNF-alpha and IL-6. Among the lipid A analogues possessing different numbers of acyl groups on a 4-O-phosphono-D-glucosamine backbone, compounds like GLA-60 that possess three tetradecanoyl (C14) groups exhibited stronger activities in the production of the mediators than compounds possessing four or two C14 groups. Time course study of the production of these mediators showed that production of NO started and peaked later than those of TNF-alpha and IL-6. Neither neutralization of TNF-alpha activity by antibody nor suppression of TNF-alpha production by pentoxifylline showed a significant suppressive effect on production of NO and IL-6 upon stimulation with LPS or lipid A analogues. Neutralization of IL-6 activity by antibody showed no significant suppressive effect on production of NO and TNF-alpha. A monosaccharide lipid A analogue (GLA-58) which exhibited no detectable agonistic activity showed a suppressive effect on the production of all three mediators upon stimulation with LPS or lipid A analogues. These results indicate that signals for NO production by LPS agonists in murine macrophages are transduced in good correlation with those for production of TNF-alpha and IL-6, although they are not transduced via production of those cytokines.
 ...
PMID:Relationship of structure and biological activity of monosaccharide lipid A analogues to induction of nitric oxide production by murine macrophage RAW264.7 cells. 982 56

CAP18 (cationic antimicrobial protein; 18 kDa) is a neutrophil-derived protein that can bind to and inhibit various activities of lipopolysaccharide (LPS). The 37 C-terminal amino acids of CAP18 make up the LPS-binding domain. A truncated 32-amino-acid C-terminal fragment of CAP18 had potent activity against Pseudomonas aeruginosa in vitro. We studied the antimicrobial and LPS-neutralizing effects of this synthetic truncated CAP18 peptide (CAP18106-137) on lung injury in mice infected with cytotoxic P. aeruginosa. To determine its maximal effect, the CAP18106-137 peptide was mixed with bacteria just prior to tracheal instillation, and lung injury was evaluated by determining the amount of leakage of an alveolar protein tracer (125I-albumin) into the circulation and by the quantification of lung edema. The lung injury caused by the instillation of 5 x 10(5) CFU of P. aeruginosa was significantly reduced by the concomitant instillation of CAP18106-137. However, the administration of CAP18106-137 alone, without bacteria, induced lung edema, suggesting that it has some toxicity. Also, the peptide did not significantly reduce the number of bacteria that had been simultaneously instilled, nor did it significantly improve the survival of the infected mice. The addition of CAP18106-137 to aztreonam along with the bacteria did decrease the level of antibiotic-induced release of inflammatory mediators including tumor necrosis factor alpha, interleukin-6, and nitric oxide and also improved the survival of the mice. Therefore, more investigations are needed to confirm the toxicities and the therapeutic benefits of CAP18106-137 as an adjunctive therapy to antibiotics in the treatment of infections caused by gram-negative bacteria.
 ...
PMID:Evaluation of antimicrobial and lipopolysaccharide-neutralizing effects of a synthetic CAP18 fragment against Pseudomonas aeruginosa in a mouse model. 983 25

We investigated the influence of HMR 3004, a new ketolide antibiotic, on the pulmonary inflammation induced by heat-killed fluorescein isothiocyanate-labeled Streptococcus pneumoniae. HMR 3004 downregulated (P < 0.05) the pneumococcus-induced release of interleukin-6 (IL-6), IL-1beta, and nitric oxide in bronchoalveolar lavage fluid. The drug limited (P < 0.05) neutrophil recruitment to lung tissues and alveoli but did not interfere with phagocytosis. HMR 3004 totally abrogated lung edema. By reducing inflammation in addition to possessing antimicrobial properties, HMR 3004 may participate in improving the outcome of bacterial pneumonia.
 ...
PMID:Immunomodulating effects of HMR 3004 on pulmonary inflammation caused by heat-killed Streptococcus pneumoniae in mice. 983 35

During the present study, thirty-eight children in Upper Egypt (less than 12years old) were admitted to Pediatric Intensive Care Unit for scorpion envenomation. They were compared with thirteen apparently healthy children of matching age as controls. The victims and controls were subjected to complete clinical examination and full blood count. The evaluations of the serum levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), nitric oxide (NO) and alpha1-antitrypsin (alpha1-AT) were performed once for the controls and twice for the victims, the first sample on admission and the 2nd sample after 24 h. All victims showed significantly higher mean values of IL-1beta IL-6, NO, alpha1-AT and leucocytic count both on admission and on follow up when compared with controls. Manifestations of mild envenomation were detected among 28.9% of the victims, while 71.1% of the victims manifested severe scorpion envenomation. The severely envenomated children showed significantly higher mean values of IL-1beta, IL-6, NO, alpha1-AT and leucocytic count both on admission and on follow up when compared with mild cases. The case fatality rate in the current study was 7.8%. The non-surviving victims showed significantly higher mean values of IL-1beta, IL-6 and leucocytic count both on admission and on follow up in comparison to the survivors. Furthermore, those fatal cases showed a non-significant decline in the studied biochemical indices on follow up after 24 h, while the survivors showed a significant decline in the serum levels of IL-6, IL-1beta, NO and alpha1-AT after 24h of post arrival to the hospital. In conclusion, these data revealed that cytokines are involved in the pathogenesis of scorpion envenomation and correlated with the severity of envenomation. This may provide a rationale for anticytokine treatment.
 ...
PMID:Serum interleukin-1beta, interleukin-6, nitric oxide and alpha1-antitrypsin in scorpion envenomed children. 983 69


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