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)

Interleukin (IL)-1 is a key cytokine in inflammatory reactions. To clarify the mechanism of inflammation in the pleural cavity, we investigated the contribution of IL-1 and its antagonism to inflammatory processes in the pleural cavity. Interleukin-1 receptor antagonist (IL-1Ra) levels as well as IL-1 beta and interferon-gamma (IFN-gamma) levels were measured by enzyme immunoassay in pleural effusions from 70 patients. Pleural macrophages were also examined as possible sources of these cytokines in 10 patients. IL-1Ra was detectable in 28 patients (40%) out of 70 patients with pleural effusions. Patients with tuberculosis had significantly higher IL-1Ra as well as IFN-gamma levels in pleural effusion than patients with lung cancer. Transudative pleural effusions had low or undetectable IL-IRa levels. On the other hand, IL-1 beta levels were low, except in cases of parapneumonic pleural effusion. Spontaneous production of IL-1Ra pleural macrophages was observed in six patients, and IL-4 significantly augmented its production. Although spontaneous production of IL-1 beta was observed in only two patients, pleural macrophages produced significant amounts of IL-1 beta in response to lipopolysaccharide in all 10 patients examined. These results suggest that interleukin-1 receptor antagonist regulates various reactions by interleukin-1 in pleural effusion, and that pleural macrophages may act in situ as a source of interleukin-1 receptor antagonist.
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PMID:Interleukin-1 receptor antagonist in pleural effusion due to inflammatory and malignant lung disease. 880 40

Extracorporeal circulation exposes blood to shear stress. In many studies, researchers reported effects of shear stress on morphology and function of various blood cells, but effects on cytokine synthesis have not been studied. The authors investigated the effect of shear stress on the synthesis of interleukin-1 beta, interleukin-1 alpha, tumor necrosis factor alpha, and interleukin-1 receptor antagonist by human peripheral blood mononuclear cells. Whole heparinized blood at room temperature was exposed to shear stresses of 50, 200, or 500 dyne/cm2 for 5 min or 30 sec, and to 980 dyne/cm2 for 5 sec. Peripheral blood mononuclear cells were then separated from sheared blood and cultured for 24 hrs with or without lipopolysaccharide or Staphylococcus epidermidis. Total (intra + extracellular) cytokine synthesis was measured by specific radioimmunoassay. Viability of cultured peripheral blood mononuclear cells, determined by trypan blue exclusion and lactate dehydrogenase release, was not significantly affected by shear stress. Shear stress without lipopolysaccharide or S. epidermidis stimulation did not affect synthesis of interleukin-1 or tumor necrosis factor alpha but did enhance synthesis of interleukin-1 receptor antagonist. Lipopolysaccharide- or S. epidermidis- induced synthesis of interleukin-1 was not significantly altered by shear stress. In contrast, lipopolysaccharide-induced tumor necrosis factor alpha synthesis increased with increasing shear stress and was significantly elevated over unsheared controls, whereas S. epidermidis-induced tumor necrosis factor alpha and lipopolysaccharide- or S. epidermidis-induced interleukin-1 receptor antagonist synthesis were not significantly enhanced by shear. Therefore, sublytic trauma, such as exposure to shear stress, affects in vitro responses of peripheral blood mononuclear cells to secondary stimuli.
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PMID:Synthesis of tumor necrosis factor alpha and interleukin-1 receptor antagonist, but not interleukin-1, by human mononuclear cells is enhanced by exposure of whole blood to shear stress. 880 59

Release and cellular contents of pro- and anti-inflammatory cytokines, neutrophilic elastase and secretory leukocyte proteinase inhibitor (SLPI) were measured with enzyme-linked immunosorbent assay in peripheral blood mono- and polymorphonuclear cells stimulated with preopsonized yeast cells or lipopolysaccharide. Tumour necrosis factor alpha (TNF alpha) was also measured with a bioassay. TNF alpha production and soluble TNF alpha receptor I (sTNF RI) were demonstrated in the environment of both cell populations. The bioassay indicated levels of TNF alpha far below those detected by ELISA. The overall secretion of cytokines and their inhibitors was found to favour an anti-inflammatory balance in the environment of the stimulated cells. The interleukin-1 receptor antagonist (IL1-ra), compared with interleukin-1 beta (IL-1 beta), dominated the secretions from both cell types with a 100- to 1000-fold excess respectively. Most of the translated IL-1 beta was not secreted but found associated with the cellular compartments. In contrast to lipopolysaccharide (LPS) stimulation, preopsonized yeast cells stimulated a massive release of elastase from neutrophil cells.
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PMID:Release of cytokines and proteases from human peripheral blood mononuclear and polymorphonuclear cells following phagocytosis and LPS stimulation. 886 69

Bacterial products [lipopolysaccharide (LPS) with Gram-negative bacteria and toxins, superantigens or cell wall fragments with Gram-positive bacteria] are the main activators of the septic shock cascade. These molecules interact with monocytes, macrophages and endothelial cells to produce inflammatory cytokines [tumour necrosis factor (TNF) and interleukins 1 and 6], and may activate other harmful pathways such as the coagulation system, complement cascade and lipid mediators. As a therapeutic strategy, antibodies directed against LPS have been well studied, although, on the whole, the clinical results have been disappointing. Other possible interventions that have not yet been tested clinically include natural intracellular antibacterial proteins (e.g. bacterial permeability-increasing protein) and high density lipoprotein (responsible for detoxifying LPS in the body). The stimulation pathway of responsive cells by bacterial products is also another possible target for intervention. Compounds under investigation include soluble CD14 and antibodies directed against CD14 or LPS binding protein. Antibodies directed against the cytokines are another option. Anti-TNF antibodies are currently being investigated, but conclusive evidence of their activity is still lacking. Soluble receptors (e.g. interleukin-1 receptor antagonist, or soluble TNF receptor) are another possibility; one soluble TNF receptor is still undergoing clinical investigation.
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PMID:The inflammatory cytokines. New developments in the pathophysiology and treatment of septic shock. 886 31

The involvement of interleukin-1 in antidipsogenic effects induced by intraperitoneal (i.p.) administration of lipopolysaccharide (0.32, 0.64 and 0.96 mg/kg) in 24-h water-deprived rats, was evaluated by injection of human interleukin-1 receptor antagonist (10, 25 and 50 micrograms/rat) into the lateral cerebral ventricle (i.c.v.). The effects of either lipopolysacharide or human interleukin-1 receptor antagonist treatment on rectal temperature of 24-h water-deprived rats, were examined. Our date show that human interleukin-1 receptor antagonist administration is able to reverse, dose dependently, fever, but not lipopolysaccharide inhibition of thirst. The reduction of pyrogenic, but not of antidipsogenic, effects of lipopolysaccharide following human interleukin-1 receptor antagonist administration suggests that lipopolysaccharide inhibition of thirst is not dependent on interleukin-1 induced fever and that interleukin-1 is not a direct mediator implicated in inhibition of water intake provoked by peripheral injection of lipopolysaccharide.
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PMID:Interleukin-1 receptor antagonist does not reverse lipopolysaccharide-induced inhibition of water intake in rat. 887 44

The host response to the presence of lipopolysaccharide (LPS) is complex and varied. Two closely related endogenous serum proteins, LPS-binding protein (LBP) and bactericidal/permeability-increasing factor (BPI), regulate delivery of LPS to CD14 antigen on effector cell surfaces and modulate the host response to LPS. In the study presented here, plasma levels of LBP and BPI were measured, predialysis, 15 min into dialysis and postdialysis in patients dialyzed with cellulose, cellulose-tri-acetate (CTA), and polysulfone dialyzers. Further, the association between LBP levels and BPI release during hemodialysis and clinical and laboratory characteristics of patients, complement activation represented by plasma C3a levels, and monocyte cytokine production represented by interleukin-1 receptor antagonist (IL-1Ra) synthesis was also studied. Predialysis plasma levels of LBP were 14,459 +/- 544, 13,889 +/- 1362 and 12,622 +/- 6305 ng/mL, respectively, with cellulose, CTA, and polysulfone dialyzers, and postdialysis levels were 17,834 +/- 861, 20,979 +/- 8485 and 18,177 +/- 1656 ng/mL, respectively. Postdialysis plasma levels of LBP were consistently higher than predialysis levels with all three dialyzers (P < 0.05). However, plasma LBP levels were not significantly different between the three dialyzers either predialysis (P = 0.28) or postdialysis (P = 2.8). There were no significant differences in predialysis BPI levels between the three dialyzers (P = 0.21). BPI levels at 15 min of dialysis with CTA (10.91 +/- 3.65 ng/mL) and polysulfone (10.73 +/- 2.24 ng/mL) dialyzers were significantly greater (P < 0.05) than that observed with cellulose (5.49 +/- 0.66 ng/mL). Similarly, postdialysis levels with CTA and polysulfone were significantly greater (P < 0.05) than that observed with cellulose dialyzers. The percentage change in BPI levels between predialysis and 15 min was 1341 +/- 243%, 2935 +/- 1033%, and 3790 +/- 1151% for cellulose, CTA, and polysulfone dialyzers, respectively. The changes in BPI levels from predialysis to 15 min and between pre- and postdialysis samples were statistically significant for all three dialyzers (P < 0.05). Postdialysis LBP:BPI ratios were 50 +/- 6%, 18 +/- 4%, and 22 +/- 6% of predialysis ratios for cellulose, CTA, and polysulfone dialyzers, respectively. These changes were statistically significant (P < 0.05) for all three dialyzers. There was no significant correlation between baseline clinical or laboratory characteristics and predialysis LBP levels. Similarly, the correlation between BPI levels at 15 min of dialysis with the clinical and laboratory characteristics was also poor, with the exception of serum albumin (r = 0.43, P = 0.008). The correlation between BPI levels at 15 min of dialysis with plasma LBP levels (r = -0.29; P = 0.08), plasma C3a levels (r = -0.1; P = 0.55), peripheral blood mononuclear cells (PBMC) content of IL-1Ra (r = 0.01; P = 0.94), and IL-1Ra production by unstimulated (r = 0.13; P = 0.45), and endotoxin-stimulated PBMC (r = 0.32; P = 0.06) was not statistically significant. The results of this study demonstrate that dialysis with cellulose, CTA, and polysulfone dialyzers results in a significant increase in LBP and BPI levels. BPI release is probably mediated by non-complement factors and may be related to the nutritional status of the patient. The release of BPI during HD and consequent lowering of the LBP:BPI ratio could potentially afford some protection against endotoxin in the dialysate.
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PMID:Lipopolysaccharide-binding protein and bactericidal/permeability-increasing factor during hemodialysis: clinical determinants and role of different membranes. 907 15

1. The objective of the present study was to determine the sites of action of the cytokine, interleukin-1 (IL-1), in the febrile response to local inflammation in the rat, by comparing the importance of IL-1 in the local tissues, the circulation and the brain. This was achieved by injecting lipopolysaccharide (LPS, 100 micrograms kg-1) into a subcutaneous air pouch and testing the effects of blocking IL-1 action with the human recombinant interleukin-1 receptor antagonist (IL-1ra) injected either into the air pouch, intraperitoneally (1 mg kg-1, 0 + 1 h, i.p.), or intracerebroventricularly (200 micrograms/rat, 0 + 1 h, i.c.v.). 2. To investigate the effect of IL-1ra on fever and the induction of local and circulating cytokines (IL-1 and IL-6), separate experiments were performed in which groups of animals were killed 1.5, 3 or 5 h after LPS injection. Plasma and pouch fluid samples were collected for bioassay of IL-1 and IL-6. 3. Injection of LPS into the air pouch significantly increased (1.5 degrees C) body temperature, local (air pouch) concentrations of bioactive IL-1 and IL-6, and circulating bioactive IL-6, compared to saline-treated controls. 4. Injection of IL-1ra into the pouch significantly attenuated LPS fever (P < 0.001). This decrease in body temperature was associated with significant inhibition of local IL-1 bioactivity 1.5 (96%), 3 (84%) and 5 h (72%), and in bioactive IL-6 in pouch lavage fluid 1.5 (45%) and 5 h (35%), after LPS injection. The concentration of bioactive IL-6 in the plasma was significantly reduced (39%) at 3 h, when temperature was approaching the maximal value. 5. Both systemic (i.p.) and central (i.c.v.) administration of IL-1ra significantly attentuated LPS fever (P < 0.05). However, it had no effect on either local concentrations of bioactive IL-1 or IL-6, or circulating IL-6, at any of the sample points. 6. These data suggest that IL-1 is released locally, at the site of tissue inflammation and that it is an important mediator of the febrile response to local inflammation. The results also indicate that IL-1 produced locally may contribute to the production of IL-6 which is released into the circulation, and that IL-1 has important actions in the generation of fever at other sites, including the brain.
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PMID:Sites of action of IL-1 in the development of fever and cytokine responses to tissue inflammation in the rat. 910 2

Concentrations and ex vivo production of interleukin 1 beta (IL-1), tumour necrosis alpha (TNF), interleukin 6 (IL-6), interleukin-1 receptor antagonist (IL-1RA) and TNF soluble receptors (sTNF-receptors, P55 and P75) were measured in bronchoalveolar lavage (BAL) fluid and blood in 23 HIV-seropositive (HIV+) patients with Pneumocystis carinii pneumonia (PCP) and compared with values found in healthy HIV-seronegative (HIV-) controls and asymptomatic HIV+ subjects. Concentrations of the proinflammatory cytokine IL-1 beta were increased in BAL fluid of HIV+ patients with PCP (184 +/- 47 pg mL-1) compared with undetectable levels in healthy control subjects (P = 0.0001). In plasma of these patients higher concentrations of the anti-inflammatory cytokine IL-1RA were found during acute PCP than after recovery (2.1 +/- 0.7 vs. 0.5 +/- 0.2 ng mL-1, P = 0.01). No correlations could be found between cytokine concentrations and clinical severity of the infection. Corticosteroid treatment did not influence cytokine concentrations in BAL or blood, nor did it suppress the production in alveolar cells. In whole-blood cultures, however, lipopolysaccharide (LPS)-stimulated production was significantly suppressed for IL-1 (1.3 vs. 5.5 ng mL-1, P = 0.009) and for IL-6 (0.6 vs. 2.5 ng mL-1, P = 0.01). The overall data show that in HIV+ patients with PCP (similar to what we had found previously in HIV-patients with PCP) proinflammatory cytokines are more prominently present in BAL, whereas anti-inflammatory reaction is predominant in the circulation.
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PMID:Cytokine profiles in bronchoalveolar lavage fluid and blood in HIV-seropositive patients with Pneumocystis carinii pneumonia. 913 83

The purpose of this study was to determine whether cytotoxic chemotherapy influences the number and function of alveolar macrophages (AM) in patients with lung cancer. AM were obtained by bronchoalveolar lavage from 24 patients with lung cancer and 17 control patients. The functional integrity of AM was determined by their ability to produce interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-1ra) before and after platinum-containing systemic chemotherapy. The productions of IL-1 beta and IL-1ra were quantitated by enzyme immunoassays. The proportions of multinucleated cells among AM were significantly decreased after systemic chemotherapy in lung cancer patients. No significant difference in spontaneous and lipopolysaccharide (LPS)-stimulated IL-1 beta or IL-1ra production by AM was observed between lung cancer patients and control patients. Significant increase of IL-1 beta and significant decrease of IL-1ra production by AM were demonstrated in patients with small cell lung cancer who experienced response to systemic chemotherapy. These results suggest that systemic chemotherapy may influence functional roles of AM in the lung, and consideration of influence of systemic chemotherapy on host functions is important in cancer treatment.
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PMID:Systemic chemotherapy alters interleukin-1 beta and its receptor antagonist production by human alveolar macrophages in lung cancer patients. 916 Mar 56

Equine interleukin-1 receptor antagonist (IL-1ra) was molecularly cloned to establish a basis for cytokine therapy of acute and chronic inflammatory diseases in the horse. cDNA clones encoding the whole coding sequence of equine IL-1ra were isolated from equine peripheral blood mononuclear cells (PBMC) that had been stimulated with lipopolysaccharide (LPS). The equine IL-1ra cDNA obtained in this study contained an open reading frame encoding 177 amino acid residues. The predicted amino acid sequence of equine IL-1ra shared 75.7, 75.3 and 76.3% similarity with sequences of human, murine and rabbit IL-1ras, respectively. An N-glycosylation site and five cysteine residues conserved in human, murine and rabbit IL-1ras were also found at the corresponding positions in equine IL-1ra. Recombinant glutathione S-transferase (GST)-equine IL-1ra fusion protein produced by Escherichia coli was purified. This protein was shown to inhibit the cytostatic or cytotoxic activity of IL-1 on A375S2 cells, indicating that the equine IL-1ra cDNA obtained in this study encodes biologically active equine IL-1ra.
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PMID:Molecular cloning and functional expression of equine interleukin-1 receptor antagonist. 922 27


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