Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously showed that injection of homogenous staphylococcal protein A-V antigen fusion peptide into mice delayed allograft rejection and suppressed the major proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) associated with generation of protective granulomas. This study was undertaken to determine if V antigen could prevent endotoxic shock, known to be mediated by excessive production of certain proinflammatory cytokines. After treatment with 50 microg of homogeneous V antigen-polyhistidine fusion peptide (Vh), the 50% lethal dose of purified lipopolysaccharide (LPS) in BALB/c mice immediately rose from 63 microg (normal controls) to 318 microg, fell to near baseline (71 microg) in 6 h, and then slowly rose to a maximum of 566 microg at 48 h before again returning to normal. Injected Vh alone (50 microg) promptly induced the anti-inflammatory cytokine interleukin-10 (IL-10) as well as modest levels of TNF-alpha (an inducer of IL-10) in spleen. Concomitant injection of Vh and an otherwise lethal dose of LPS (200 microg) dramatically decreased levels of TNF-alpha and IFN-gamma in the spleen and peritoneal lavage fluid as compared to values determined for LPS alone. These results would be expected if V antigen directly up-regulated IL-10 that is reported to generally down-regulate proinflammatory cytokines. Mice receiving 200 microg of LPS 48 h after injection of Vh exhibited patterns of cytokine synthesis similar to those observed in endotoxin-tolerant mice, a condition also reported to be mediated by IL-10. These findings suggest that V antigen serves as a virulence factor by amplifying IL-10, thereby repressing proinflammatory cytokines required for expression of cell-mediated immunity.
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PMID:Resistance to lipopolysaccharide mediated by the Yersinia pestis V antigen-polyhistidine fusion peptide: amplification of interleukin-10. 911 51

Intracellular cyclic nucleotide levels play an important role in the regulation of several immunological processes. Since elevation of intracellular cyclic adenosine monophosphate and/or cyclic guanosine monophosphate concentration by inhibition of phosphodiesterase (PDE) is known to modulate the inflammatory response, we compared the effect of amrinone, an inhibitor of the PDE III isoenzyme, and of theophylline, a nonspecific PDE inhibitor, on the plasma tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10), and nitric oxide response in mice to intraperitoneal injection of bacterial lipopolysaccharide (LPS). Intraperitoneal treatment of animals with amrinone (100 mg/kg) 30 min before LPS administration decreased both plasma IL-6 and IL-10 concentrations in the first phase of the response, but enhanced plasma levels of these cytokines in the second part. In contrast, pretreatment of the animals with theophylline (100 mg/kg) enhanced LPS-induced plasma IL-6 and IL-10 levels during the whole response. However, pretreatment with both PDE inhibitors resulted in a marked inhibition of LPS-evoked plasma concentrations of TNF-alpha and nitrite/nitrate (breakdown products of nitric oxide) throughout the response. This study demonstrates for the first time that amrinone and theophylline possess differential, but primarily anti-inflammatory, properties during LPS-induced systemic inflammation in the mouse.
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PMID:Amrinone and theophylline differentially regulate cytokine and nitric oxide production in endotoxemic mice. 916 73

Intracerebroventricular (i.c.v.) interleukin-10 (25, 50, and 100 ng/rat) effects on water intake, exploratory behaviour, and rectal temperature were evaluated in rats treated intraperitoneally (i.p.) with lipopolysaccharide (0.32, 0.64, and 0.96 mg/kg). Endotoxin administration induced fever and inhibition of thirst in water-deprived rats, and a decrease in lococomotory activity in normohydrated and water-deprived animals. Our data show that interleukin-10 during lipopolysaccharide administration controlled fever, increases exploratory behaviour, but did not reverse lipopolysaccharide inhibition of thirst. These effects suggest that fever, depression in locomotory activity but not inhibition of thirst, induced by endotoxin are influenced by interleukin-10 levels.
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PMID:Effects of interleukin-10 on water intake, locomotory activity, and rectal temperature in rat treated with endotoxin. 922 77

The present study concerns the effect of the xanthine derivates lisofylline (LSF) and pentoxifylline (PTX) on the production of pro-inflammatory cytokines tumour-necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) and the de-activating cytokine interleukin-10 (IL-10) by human leucocytes during stimulation with lipopolysaccharide (LPS), heat-killed Gram-negative bacteria (GNB) or Gram-positive bacteria (GPB). The production of TNF-alpha and IL-1 beta by leucocytes stimulated with LPS, Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae was inhibited by both drugs. The production of IL-10 by leucocytes stimulated with LPS and Hib was inhibited by both xanthine derivates only at 48 hr. However, incubation of leucocytes with S. pneumoniae in the presence of LSF or PTX stimulated the production of IL-10 about four- and twofold at 24 hr and 48 hr, respectively. In all instances, the extent of inhibition or enhancement of cytokine production by LSF or PTX was equal. The divergent effects of xanthine derivates on the IL-10 production indicate the existence of distinct intracellular pathways depending on whether leucocytes are stimulated by GPB or GNB.
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PMID:Effect of lisofylline and pentoxifylline on the bacterial-stimulated production of TNF-alpha, IL-1 beta IL-10 by human leucocytes. 922 16

Acute lung injury is the end result of common pathways initiated by a variety of local or systemic insults leading to diffuse damage to the pulmonary parenchyma. Despite the accumulation of abundant information regarding the physiological and cellular basis of lung injury and increasingly sophisticated intensive care, an improvement in prognosis has lagged behind. It has become clear that there is not one mediator responsible for acute lung injury but rather a complex interplay exists between diverse proinflammatory (eg, lipopolysaccharide, complement products, cytokines, chemokines, reactive oxygen species, and eicosanoids) and anti-inflammatory (interleukin-10, interleukin-1-RA, PGI2) mediators. It is essential that we obtain a better understanding of the complexities of the acute inflammatory response if we are to successfully intervene to prevent or ameliorate tissue injury. The purpose of this review is to summarize recent developments that have contributed to our understanding of the basic mechanisms of lung injury. We focus on the persistence of the inflammatory response on a local and systemic level, including local mechanisms acting within the alveolar space regulating synthesis, release, and activation of inflammatory mediators; the balance of proteinases and antiproteinases; the abnormalities of surfactant; and the potential importance of endogenously released anti-inflammatory mediators. It is hoped that the results of these studies will provide insights into the pathogenesis of lung injury and lead to novel therapeutic strategies to prevent or ameliorate lung injury.
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PMID:Mechanisms of acute lung injury. 923 71

Monophosphoryl lipid A (MPL) is a nontoxic derivative of the lipid A region of lipopolysaccharide (LPS) that is being developed as both an adjuvant and prophylactic drug for septic shock. We compared the ability of LPS and MPL to induce interleukin-10 (IL-10), IL-12 p35, IL-12 p40, gamma interferon (IFN-gamma), glucocorticoid receptor (GR), IL-1 receptor antagonist (IL-1ra), and inducible nitric oxide synthase mRNA expression in murine peritoneal macrophages. These genes were chosen for their ability to positively or negatively regulate the host immune response and thus for their potential involvement in MPL-induced adjuvanticity or in its ability to protect against sepsis. LPS was a more potent inducer of IL-12 p35, IL-12 p40, and IFN-gamma mRNA, as well as of IL-12 protein, than MPL. In contrast, MPL induced higher levels of IL-10 mRNA than did LPS from 1 to 1,000 ng/ml. In general, MPL was not a more potent inducer of negative regulatory genes, since MPL and LPS induced similar levels of GR and IL-1ra mRNA. Addition of anti-IL-10 antibody to cultures increased the induction of MPL-induced IL-12 p35, IL-12 p40, and IFN-gamma mRNA, suggesting that the enhanced production of IL-10 by MPL-stimulated macrophages contributes to decreased production of mRNA for IL-12 (p35 and p40) and IFN-gamma. Conversely, the addition of exogenous IL-10 to LPS-treated macrophages reduced the mRNA expression of these cytokine genes. These studies suggest that enhanced production of IL-10 by MPL-stimulated macrophages may contribute to the reduced toxicity of MPL through its negative action on induction of cytokines shown to enhance endotoxicity.
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PMID:Lipopolysaccharide and monophosphoryl lipid A differentially regulate interleukin-12, gamma interferon, and interleukin-10 mRNA production in murine macrophages. 923 81

Interleukin-10 inhibits T-lymphocyte activation and proliferation and lipopolysaccharide-induced monocyte production of proinflammatory cytokines. Fifty-four healthy volunteers received single doses of recombinant human interleukin-10 (1.0, 2.5, 5.0, 10, 25, or 50 micrograms/kg) or placebo by subcutaneous injection (randomized double-blind assignment). Clinical adverse events were infrequent at doses below 50 micrograms/kg (five of six subjects had mild flu-like syndrome). Mean serum interleukin-10 concentrations were dose related. The mean terminal-phase half-life ranged from 2.7 to 4.5 hours, and the apparent volume of distribution ranged from 0.70 to 1.35 L/kg. Hematologic changes included transient mild to moderate increases of neutrophil counts, decreases of lymphocyte counts, and a delayed decrease of platelet counts. Recombinant human interleukin-10 significantly suppressed production of the proinflammatory cytokines interleukin-1 beta and tumor necrosis factor-alpha by whole blood stimulated ex vivo with Escherichia coli lipopolysaccharide.
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PMID:Pharmacodynamics of subcutaneous recombinant human interleukin-10 in healthy volunteers. 928 53

The lethal effects occurring in neonatal (<24-h-old) BALB/c mice after challenge with 25 mg of lipopolysaccharide (LPS) per kg of body weight were significantly counteracted by pretreatment with recombinant interleukin-10 (rIL-10; 25 or 50 ng/mouse). Concordantly, blockage of endogenous IL-10 with the SXC1 monoclonal antibody increased LPS-induced mortality. Both IL-10 and SXC1 modulated the release of tumor necrosis factor alpha (TNF-alpha) so that, relative to controls, peak TNF-alpha values after LPS challenge were decreased by rIL-10 and increased by anti-IL-10.
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PMID:Endotoxin-induced lethality in neonatal mice is counteracted by interleukin-10 (IL-10) and exacerbated by anti-IL-10. 930 14

Idiopathic pulmonary fibrosis (IPF) and bronchiolitis obliterans with organizing pneumonia (BOOP) are interstitial lung diseases of unknown pathogenesis. Alveolar macrophages play a major role in the regulation of the inflammatory response in these diseases through their ability to produce cytokines that modify the inflammatory response. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) exhibit proinflammatory and anti-inflammatory actions, respectively, and thus an imbalance in the expression of these cytokines may contribute to the pathogenesis of IPF and BOOP. Therefore, we quantified IL-10 and TNF-alpha mRNA levels in alveolar macrophages obtained by bronchoalveolar lavage (BAL) from patients with IPF and BOOP and in normal healthy volunteers. The level of TNF-alpha mRNA in macrophages obtained from IPF and BOOP patients was not significantly different from normal healthy subjects. However, macrophages from patients with IPF and BOOP expressed increased levels of IL-10 mRNA compared with healthy controls. In addition, stimulation of alveolar macrophages with lipopolysaccharide in the presence of a neutralizing anti-IL-10 antibody augmented the production of TNF-alpha over that seen in the absence of anti-IL-10 antibody, suggesting that the increased expression of IL-10 by alveolar macrophages may act to control the expression of TNF-alpha. Paradoxically, measurement of IL-10 protein in cell-free BAL fluid revealed lower amounts of the protein in patients with IPF and BOOP compared with healthy controls.
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PMID:Increased expression of the interleukin-10 gene by alveolar macrophages in interstitial lung disease. 931 4

In a previous study we have demonstrated in conscious endotoxemic mice that isoproterenol, a nonselective agonist of beta-adrenergic receptors, decreased the production of proinflammatory mediators tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO), and enhanced the formation of the anti-inflammatory cytokine interleukin-10 (IL-10). In the present study we investigated the effect of isoproterenol on the bacterial lipopolysaccharide (endotoxin, LPS; 10 microg/ml)-induced inflammatory response in RAW 264.7 macrophages in vitro. Pretreatment of cells with isoproterenol (10-300 microM) resulted in an inhibition of TNF-alpha, NO (reflected as its stable breakdown product nitrite), as well as IL-10 production that was paralleled with a restoration of the LPS-induced suppression of mitochondrial respiration. In addition, isoproterenol elevated cAMP accumulation in these cells. Finally, isoproterenol (300 microM) did not influence the nuclear translocation of nuclear factor kappaB. These data demonstrate that isoproterenol potently downregulates the LPS-induced inflammatory response and further support the notion that stimulation of beta-adrenoreceptors can be an effective strategy in the treatment of inflammatory diseases.
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PMID:Isoproterenol inhibits Il-10, TNF-alpha, and nitric oxide production in RAW 264.7 macrophages. 944 38


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