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)

1. The long-acting beta 2-adrenoceptor agonist, salmeterol has been evaluated for its anti-inflammatory effects in the guinea-pig lung and skin. 2. Salmeterol, administered in bronchodilator doses to conscious guinea-pigs by both oral (0.01-1.0 mg kg-1) and inhaled (nebulizer concentration, 0.001-1.0 mg ml-1) routes, inhibited histamine-induced plasma protein extravasation (PPE) into the airway lumen. 3. Inhibition of PPE by salmeterol was long-lasting (greater than 6 h) and was inhibited by prior administration of propranolol (1 mg kg-1, s.c.), indicating an effect mediated by beta-adrenoceptors. 4. Inhaled salbutamol (nebulizer concentration, 0.001-1.0 mg ml-1) also inhibited PPE in guinea-pig lung but, in contrast to salmeterol, this effect was short-lived with substantial loss of activity 2 h after administration. 5. Inhaled salmeterol (0.1 mg ml-1) and salbutamol (1.0 mg ml-1) inhibited the accumulation of neutrophils in guinea-pig lung in response to lipopolysaccharide (100 micrograms ml-1). Salmeterol, but not salbutamol, inhibited the infiltration of eosinophils into the airway lumen in response to platelet activating factor (100 micrograms ml-1). These effects of salmeterol were blocked by prior administration of propranolol (5 mg kg-1, s.c.), indicating that they were also beta-adrenoceptor-mediated. 6. Oral salmeterol (10 mg kg-1, p.o.), but not salbutamol (10 and 100 mg kg-1, p.o.), inhibited zymosan-induced granulocyte accumulation and PPE in guinea-pig skin. Lower doses of salmeterol (0.1 and 1 mg kg-1) inhibited PPE, but not granulocyte accumulation.The effects of salmeterol were blocked by prior administration of propranolol (1mgkg-', s.c.). Both salmeterol and salbutamol inhibited histamine-induced PPE in guinea-pig skin.7. Intradermal salmeterol (10-'mol per site), but not salbutamol, was also effective in inhibiting zymosan-induced granulocyte accumulation and PPE in guinea-pig skin.8. It is concluded that salmeterol, at bronchodilator doses in the guinea-pig, inhibits granulocyte accumulation and PPE, possibly by an action on the vasculature. As this profile of activity is not shared by the shorter-acting compound, salbutamol, it would seem that anti-inflammatory activity is associated with beta-adrenoceptor agonism of long duration. The implications of these findings for the use of salmeterol in the treatment of bronchial asthma are discussed.
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PMID:Inhibition by salmeterol of increased vascular permeability and granulocyte accumulation in guinea-pig lung and skin. 135 36

Inhalation of 20 micrograms endotoxins (from the membrane of Gram-negative bacteria) has been reported to induce a bronchial obstructive response in asthmatic subjects. The aim of the present study was to evaluate in asthmatic patients the possibility of an inflammatory response to inhaled endotoxins. Eight patients with mild asthma were submitted to bronchial challenge tests, in a single-blind trial, on Day 1 with control solution and on Day 7 with 20 micrograms endotoxin of Escherichia coli (026:B6). Local inflammatory response was indirectly evaluated by the degree of bronchial hyperresponsiveness (BHR) expressed as PD20 FEV1 histamine (the dose of histamine inducing a 20% decrease in FEV1) at 0, 6, 24, and 48 h and 7 days. Systemic inflammation was investigated by sequential blood determinations of total (and differential) white cells, complement anaphylatoxin C5a, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and C-reactive protein (CRP). A significant (p < 0.01) bronchial obstructive response was demonstrable 45 min after lipopolysaccharide (LPS) inhalation, lasting 5 h. Comparing the level of BHR after control inhalation, a significant (p < 0.05) increase in BHR was shown 6 h after LPS, partially normalized at 24 and 48 h. A short peak in TNF-alpha at 60 min (p < 0.05) and an increase in total white blood cells (p < 0.01) and neutrophil polymorphonuclear neutrophils at 360 min (p < 0.05) and of CRP at 24 and 48 h (p < 0.05 and p < 0.01) were significant. The other blood parameters did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inflammatory response to acute inhalation of endotoxin in asthmatic patients. 148 24

Peripheral blood monocytes (PBM) may be activated in asthmatic patients, a condition usually reverted by corticosteroid (CS) treatment. In the present research we have evaluated the spontaneous or lipopolysaccharide (LPS)-induced production of interleukin 1 (IL-1) and tumour necrosis factor (TNF) by PBM obtained from 14 asthmatic subjects during an asthmatic attack and after 1 week of CS treatment. The control group included 20 healthy volunteers. PBM obtained during severe asthma showed a pattern of IL-1 and TNF secretion similar to that of normal subjects. After CS treatment, IL-1 levels did not change significantly in comparison to baseline values, while LPS-induced TNF production was apparently related to the degree of airway obstruction after CS treatment. In fact, TNF production by PBM from CS-responsive subjects was significantly decreased in comparison to the levels determined before CS treatment, while PBM from CS-resistant subjects produced the same cytokine levels regardless of CS treatment. The present study suggests that the determination of LPS-induced TNF secretion by PBM could be used to confirm the effectiveness of CS treatment in asthma.
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PMID:Effect of corticosteroid treatment on interleukin-1 and tumour necrosis factor secretion by monocytes from subjects with asthma. 158 71

A longitudinal study was conducted to determine the pathogenesis and effect of immunotherapy (IT) on monocyte function. Production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) by peripheral blood monocytes in 31 asthmatic children before and one year after IT was compared. Twenty-two children completed the treatment course, and 13 age-matched healthy children served as controls. Adherent monocytes were isolated and stimulated with either crude mite extract of Dermatophagoid farinae (Df) for 7 days or lipopolysaccharide (LPS) for 3 days. The amount of TNF and IL-1 in culture supernatant was quantified by TNF and IL-1 enzyme-linked immunosorbent assay (ELISA) kits, respectively. The LPS-stimulated TNF production in patients was not different before or after IT (245.8 +/- 110.9 vs. 213.3 +/- 161.6 pg/0.1 ml, p +/- 0.202), but was significantly higher than the control (66.7 +/- 42.7 pg/0.1 ml; p less than 0.0001). The LPS-stimulated IL-1 production was similar among the three groups. When stimulated with Df antigen, monocytes from asthmatic patients produced a greater amount of TNF and IL-1 than did those from the control (p less than 0.001). Furthermore, although the production of TNF decreased after successful IT (360.2 +/- 181.6 vs 243.9 +/- 189.1 pg/0.1 ml, p less than 0.05), the production of IL-1 did not change (679.9 +/- 254.1 vs. 534.8 +/- 257.6 pg/0.1 ml, p greater than 0.05). Thus, repeated long-term administration of allergen (IT) was able to suppress specifically the TNF, but not IL-1 production of monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
J Asthma 1992
PMID:The effect of immunotherapy on interleukin-1 and tumor necrosis factor production of monocytes in asthmatic children. 160 37

The effects of representatives of three classes of compounds were investigated on antigen-induced bronchopulmonary eosinophilia in sensitized Brown-Norway rats. Rats were sensitized by 3 weekly inhalation provocations with aerosols of ovalbumin. Twenty-four hours after a fourth weekly antigen provocation, cell populations were enumerated following bronchoalveolar lavage (BAL) in animals treated with test compounds or the appropriate vehicle. A marked eosinophil-rich influx of inflammatory cells into the bronchial lumen followed the antigen provocation in sensitized animals. Dose-related inhibitions of antigen-induced lung eosinophilia were demonstrated with: 1) glucocorticoids, given po (methylprednisolone acetate, U-8210) or by inhalation (methylprednisolone suleptanate, U-67590A); 2)the non-glucocorticoid 21-amino steroid, U-75412E, and 3) the leukotriene B4 antagonist, U-75302. The steroids methylprednisolone and U-75412E were tested for glucocorticoid activity using phorbol ester-differentiated U937 (human macrophage) cells. Methylprednisolone but not U-75412E produced a dose-dependent inhibition of lipopolysaccharide-stimulated thromboxane synthesis by the U937 cells. Leukotriene B4 antagonists and the novel 21-aminosteroid, U-75412E, which lacks glucorticoid activity, provide leads for the development of compounds which inhibit the chronic airway inflammation associated with asthma in man.
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PMID:Novel inhibitors of pulmonary eosinophil accumulation. 166 9

A thymocyte proliferative response assay was used to compare spontaneous and lipopolysaccharide (LPS)-induced interleukin-1 (IL-1) release by alveolar macrophage (AM) in asthmatic patients and normal subjects. Twelve asthmatic patients and seven nonsmoking healthy subjects underwent a bronchoalveolar lavage (BAL). All asthmatic patients had a reversible airway obstruction and 7/12 were allergic. BAL AM were separated by adherence on tissue culture plates in medium RPMI-1640 supplemented with antibiotics and fetal calf serum, and were incubated with or without 10 micrograms/ml LPS for 20 h. Free-cell supernatants were tested by C3H/HeJ mice thymocyte proliferative assay. Unstimulated AM supernatant IL-1 activity was significantly higher in asthmatic patients (mean +/- SEM: 47.8 +/- 11.9 units/10(6) AM) in comparison with healthy subjects (4.8 +/- 2.3 units/10(6) AM; p less than 0.05, Mann-Whitney U test) but did not significantly differ between allergic (42.2 +/- 15.5 units/10(6) AM) and intrinsic asthmatic patients (55.8 +/- 20.7 units/10(6) AM). For healthy subjects, IL-1 activity was significantly higher in LPS-stimulated AM supernatants (85 +/- 20 units/10(6) AM, p less than 0.05; Mann-Whitney U test) in comparison with unstimulated ones; for asthmatic patients, unstimulated and LPS-stimulated AM supernatant IL-1 activity did not significantly differ. This finding is in accordance with previous work suggesting that AM from asthmatic patients have a weak suppressive activity upon lymphocyte proliferation and emphasize the enhanced AM releasability in asthma.
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PMID:Interleukin-1 release by alveolar macrophages in asthmatic patients and healthy subjects. 234 Dec 2

Preincubation of human basophils with bacterial lipopolysaccharide (LPS) purified from the heptose-deficient mutant Salmonella minnesota R595 enhanced by an average of sixfold the response of peripheral blood basophils obtained from allergic donors to several allergens in vitro as judged by release of histamine. Enhancement occurred at suboptimal, optimal, and supraoptimal concentrations of antigen. No effect was seen if basophils were from a nonallergic donor, and LPS by itself rarely caused histamine release from any preparation of basophils. However, histamine release in basophils from nonallergic donors induced by antibody directed against IgE (anti-IgE) also was enhanced by LPS. Potentiation of histamine release occurred if basophils were pretreated with LPS before addition of anti-IgE for as little as 5 min; there was no increase in release if anti-IgE and LPS were added simultaneously to cells. LPS enhanced the rate of release without altering duration of the release response. LPS potentiation of release of histamine by F(ab')2 fragments of anti-IgE was equivalent to its effect on release triggered by the intact antibody molecule, confirming that the effect of LPS is not due solely to its interaction with the Fc component of the anti-IgE. These data thus provide evidence for modulation of basophil response to IgE-mediated stimuli by LPS, resulting in a significant enhancement of response. Enhancement by LPS appears to be independent of the stimulus which triggers the IgE receptor. The contribution of this mechanism to allergic disease or asthma remains to be determined.
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PMID:The effect of bacterial lipopolysaccharide (LPS) on histamine release from human basophils. I. Enhancement of immunologic release by LPS. 257 9

Monocytes from 6 patients with asthma and positive bronchial challenge with extract from the house dust mite Dermatophagoides pteronyssinus (Dp) were stimulated with lipopolysaccharide (LPS) and allergen extract from Dp. In order to neutralize putative endotoxin contamination of the allergen extract, some cultures were incubated in the presence of polymyxin B. Interleukin-1 (IL-1) activity was assayed by the comitogenic activity of the crude monocyte supernatants on phytohemagglutinin-stimulated murine thymocytes. Our results suggest that, upon stimulation with LPS and allergen, monocytes from atopic patients possess a normal capacity to produce IL-1. Like monocytes from healthy controls, patient monocytes do not produce IL-1 spontaneously. The specificity of the allergen stimulus is not well-defined, and further characterization of the IL-1-inducing property awaits the availability of endotoxin-free allergen preparations.
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PMID:Interleukin-1 production by monocytes from patients with allergic asthma after stimulation in vitro with lipopolysaccharide and Dermatophagoides pteronyssinus mite allergen. 325 87

Airway inflammation is an important aspect of asthma. Recent studies of airway inflammation in asthma have focused attention on cytokines released by T helper lymphocyte type 1 (Th1)- and Th2-like T cells. Interleukin (IL)-1 is also increased in the airways of asthmatics, and it is most likely derived from airway and alveolar macrophages. The effects of Th1 or Th2 cytokines on the release of IL-1 or its specific antagonist, IL-1ra, have not been well studied. We examined the response of THP-1 cells, a myelomonocytic cell line, to stimulation with various Th1 and Th2 cytokines and found that IL-4, IL-10, and IFN-gamma increased IL-1ra mRNA and protein release. The increase in mRNA was not due to an increase in IL-1ra mRNA stability. IL-4 (10 ng/ml) increased IL-1ra release from 9,641 +/- 322 [from cells stimulated with lipopolysaccharide (LPS) alone] to 50,796 +/- 1,917 pg/ml (from cells stimulated with LPS and IL-4). IL-10 (10 ng/ml) caused a similar upregulation of IL-1ra from LPS-stimulated cells: 87,478 +/- 7,808 compared with 8,004 +/- 1,166 pg/ml released from the cells stimulated with LPS alone. Cells stimulated with IFN-gamma (100 U/ml) and LPS released 27,854 +/- 3,626 pg/ml of IL-1ra, compared with 9,069 +/- 236 pg/ml in the presence of LPS alone. In addition, the Th1 cytokine, IFN-gamma, but not the Th2 cytokines, IL-4 and IL-10, upregulated IL-1 beta mRNA and increased the release of IL-1 beta protein. Similar studies were performed using freshly isolated monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of interleukin-1 receptor antagonist by Th1 and Th2 cytokines. 763 20

We have developed an experimental model for exercise-induced asthma (EIA) using conscious guinea pigs. Respiratory resistance (Rrs) was measured before and after exercise (running). When a 0.05% lipopolysaccharide (LPS) was inhaled by guinea pigs which had been pretreated with a corticosteroid biosynthesis inhibitor metyrapone (50 mg/kg, i.v.), Rrs significantly increased 24 h after exercise. Metyrapone had no effect, however, on the LPS-induced increase in the numbers of macrophages, eosinophils, neutrophils and lymphocytes in bronchoalveolar lavage fluid (BALF). In order to examine the role of airway inflammation, the effects of murine recombinant interleukin-5 (mrIL-5) and platelet activating factor (PAF) were investigated in guinea pigs. The exercise-elicited increase in Rrs was observed 24 h later than the treatment with mrIL-5 in metyrapone-treated animals. The number of macrophages, eosinophils and neutrophils increased in the BALF of mrIL-5-treated animals. In contrast, a 0.05% PAF aerosol caused an increased number of eosinophils in BALF, but did not affect Rrs after exercise in either metyrapone-treated or non-treated animals. Moreover, to evaluate the value of this model as a pharmacological tool, the effect of ketotifen and prednisolone on the exercise-induced increase in Rrs was investigated. Prior administration of ketotifen and prednisolone showed a tendency to prevent, or clearly inhibited, the exercise-induced increase in Rrs in animals treated with the combination with LPS and metopyrone.
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PMID:Increase in respiratory resistance after exercise in conscious guinea pigs. As a model for exercise-induced asthma. 773 47


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