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)

Modification of the cellular immune response in uraemia is partly responsible for the increased susceptibility to infection found in dialysis patients. In order to study this further we have evaluated the in vitro production of tumour necrosis factor (TNF) by peripheral-blood monocytes (PBMCs) to stimulation by lipopolysaccharide (LPS) from dialysis patients with end-stage renal failure. The patients were subdivided into two groups according to the type of dialysis: those undergoing haemodialysis (HD; n = 12) and continuous ambulatory peritoneal dialysis (CAPD; n = 18). Results were compared with those of controls taken from healthy laboratory staff (n = 7). The experiments show that the secretion of TNF by of TNF by PBMCs in response to LPS is significantly augmented in patients undergoing HD when compared to those on CAPD (81.3 +/- 38.7 vs. 18.2 +/- 13.3 U/ml, mean +/- SD, p less than 0.001) and controls (81.3 +/- 38.7 vs. 18.1 +/- 6.6 U/ml, p less than 0.001). There was no significant difference between the CAPD group and controls. In vitro production of TNF fell slightly following a single HD session (81.3 +/- 38.7 U/ml before HD and 50.5 +/- 28.7 U/ml after HD, p less than 0.05). We conclude from this study that TNF release from PBMCs is augmented in patients with chronic renal failure receiving chronic HD but not in a similar group receiving CAPD, in vitro. TNF release, however, is suppressed immediately following a single HD session. We suggest that HD rather than uraemia per se up-regulates monocyte secretion of TNF in vitro and that this is not an immediate response to activation by membrane polymer.
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PMID:Evaluation of the in vitro production of tumour necrosis factor by monocytes in dialysis patients. 180 56

We have previously reported low serum levels of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and increased 1,25-(OH)2D3 production after the administration of 25-hydryoxyvitamin D (25OHD) to anephric humans. Since normal alveolar macrophages are known to synthesize 1,25-(OH)2D3 when stimulated with gamma-interferon or lipopolysaccharide, we determined whether macrophages derived from peripheral blood monocytes could be an extrarenal source of 1,25-(OH)2D3. Our results demonstrated that macrophages from normal individuals synthesize 1,25-(OH)2D3. The apparent Km for 25OHD3 was 6.6 +/- 0.5 nM and the maximum velocity was 47.4 +/- 13.7 fmol 1,25-(OH)2D3/h.microgram DNA. The activity of this enzyme was reduced 37.2 +/- 3.1% by physiological concentrations (96 pmol/L) of 1,25-(OH)2D3 in the incubation medium. Normal macrophages further hydroxylated 1,25-(OH)2D3 to more polar metabolites, and this catabolic activity was significantly enhanced by physiological concentrations of 1,25-(OH)2D3. In chronic renal failure, peripheral macrophages exhibited an enhanced 1 alpha-hydroxylase activity (8.2 +/- 0.8 vs. 4.2 +/- 0.5 fmol 1,25-(OH)2D3/microgram DNA.h in controls) and a decreased capacity to degrade 1,25-(OH)2D3. Exogenous 1,25-(OH)2D3, in physiological concentrations, reduced 1,25-(OH)2D3 synthesis to a degree (23.6 +/- 8.5%) comparable to that observed in normal cells. 1,25-(OH)2D3 production by macrophages did not correlate with the severity of hyperparathyroidism. Moreover, human PTH-(1-34) in supraphysiological concentrations (20,000 and 100,000 ng/L) did not stimulate the 1 alpha-hydroxylase activity of macrophages from either normal or uremic subjects. These results demonstrate that 1) normal peripheral macrophages metabolize 25OHD3 and 1,25-(OH)2D3; 2) macrophages in uremia display higher rates of 1,25-(OH)2D3 synthesis and lower rates of catabolism than normal macrophages; and 3) 1,25-(OH)2D3 deficiency, but not hyperparathyroidism, may play a role in the stimulation of 1,25-(OH)2D3 production by macrophages in chronic renal failure.
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PMID:Extrarenal production of calcitriol in normal and uremic humans. 198 15

Cellular release of cytokines may be responsible for certain complications of extracorporeal dialysis including the increased susceptibility to infection found in dialysis patients. In order to study this further, we have evaluated the in vitro production of tumor necrosis factor (TNF) by peripheral blood monocytes (PBMC) to stimulation by lipopolysaccharide (LPS) from dialysis patients with end-stage renal failure (ESRF). The patients were subdivided into two groups according to the type of dialysis; those undergoing hemodialysis (HD) (N = 12) and those performing continuous ambulatory peritoneal dialysis (CAPD) (N = 9). Results were compared with those of controls taken from healthy laboratory staff (N = 7). The experiments show that the secretion of TNF by PBMC's in response to LPS is significantly augmented in patients undergoing HD when compared to those on CAPD (81.3 +/- 38.7 U/ml vs. 18.2 + 13.3 U/ml, mean +/- SD, P < 0.001); and controls (81.3 +/- 38.7 U/ml vs. 18.1 +/- 6.6 U/ml, P < 0.001). There was no significant difference between the CAPD group and controls. In vitro monocyte production of TNF fell following a single HD session (81.3 +/- 38.7 U/ml before HD and 50.5 +/- 28.7 U/ml after HD, P < 0.05). We conclude from this study that TNF release from PBMC's in vitro is augmented in patients with chronic renal failure receiving chronic HD but not in a similar group receiving CAPD. Interestingly, TNF release from monocytes collected immediately following a dialysis was suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro production of tumor necrosis factor by monocytes cultured from dialysis patients. 832 Sep 27

Expression of CD14 on peripheral blood monocytes and serum levels of the 53 kD soluble CD14 antigen were investigated in patients with end-stage renal failure who were undergoing chronic hemodialysis (HD) with either cuprophane/hemophane (CU/HE) low-flux (LF) or polysulfone/polyamide (PS/PA) high-flux (HF) membranes. Baseline expression of CD14 was significantly lower in HD patients compared to uremic patients and normal controls. Patients using PS/PA membranes disclosed a further decreased CD14 expression than patients with CU/HE membranes. Specific fluorescence intensity for CD14 increased 15 minutes after the start of the dialysis session and was on average 22% higher after hemodialysis. The serum levels of sCD14 were elevated about 2.5-fold in HD patients compared to healthy controls (5.4 +/- 1.3 vs. 2.2 +/- 0.5 mg/liter, P < 0.0001) and were significantly higher compared to non-dialyzed patients with chronic renal failure (3.9 +/- 1.0 mg/liter, P < 0.001). After regular dialysis with high-flux membranes, soluble CD14 serum concentrations significantly increased (P < 0.001) compared to pre-dialysis levels. Values of soluble CD8 (54 kD) were elevated only 1.5-fold in HD patients relative to healthy controls, whereas serum levels of the low molecular weight soluble CD23 (20 kD) 12 and 19-fold in patients treated with HF-HD and LF-HD, reflecting the renal impairment and filtration through HF membranes. Thus, high sCD14 values in HD patients may stem from increased release of the up-regulated membrane antigen due to monocyte activation during hemodialysis treatment. Since the CD14 antigen is involved in LPS-induced monocyte activation, the influence of lipopolysaccharide on CD14 expression and sCD14 release was investigated in vitro. Addition of 1 ng/ml or 0.01 ng/ml LPS to whole blood significantly enhanced monocyte CD14 expression after 30 or 60 minutes of incubation. The release of soluble CD14 by cultured peripheral blood monocytes significantly increased in the presence of 0.01 ng/ml LPS during a five-day incubation experiment. Our results demonstrate an enhanced expression of CD14 by monocytes after HD and increased sCD14 serum levels possibly due to chronic exposure to trace amounts of endotoxins, as supported by in vitro experiments.
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PMID:Monocyte cell-surface CD14 expression and soluble CD14 antigen in hemodialysis: evidence for chronic exposure to LPS. 854 3

We investigated the cell content and production of IL-1beta and IL-1 receptor antagonist (Ra) by unstimulated and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) obtained from 15 undialyzed patients with chronic renal failure (CRF; estimated GFR <10 ml/min), 15 patients on chronic hemodialysis (HD) and 15 healthy controls. These cytokines were measured by ELISA. The cell content of IL-1beta in freshly obtained PBMC was not detectable in any group. In contrast, that of IL-1Ra in CRF (1,807 +/- 370 pg/ml, p < 0.05) as well as in HD (1,791 +/- 151 pg/ml, p < 0.001) was significantly higher than that of the controls (907 +/- 156 pg/ml). In unstimulated cultured PBMC, spontaneous production of IL-1beta in CRF (66 +/- 13 pg/ml, p < 0.05) and in HD (81 +/- 29 pg/ml, p < 0.05) was significantly higher than that of the controls (26 +/- 3 pg/ml). In contrast, comparison of spontaneous production of IL-1Ra in the three groups was not significantly different. In LPS-stimulated PBMC, IL-1beta production in CRF (10,896 +/- 1,359 pg/ml, p < 0.01)and in HD(11,441 +/- 1,400 pg/ml, p < 0.01) was significantly higher than that of the controls (6,117 +/- 572 pg/ml). However, IL-1Ra production by LPS-stimulated PBMC in the three groups was not significantly different. Moreover, the spontaneous IL-1Ra/IL-1beta production ratio in CRF (140 +/- 16, p < 0.01) and in HD (142 +/- 19, p < 0.01) was significantly lower than that of the controls (294 +/- 41). The present study demonstrates that cytokine production by PBMC in undialyzed CRF patients as well as in hemodialyzed patients is heightened and may induce impaired function of the immunological system before CRF patients are introduced to dialysis.
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PMID:Increased production of interleukin-1beta and interleukin-1 receptor antagonist by peripheral blood mononuclear cells in undialyzed chronic renal failure. 917 Dec 96

Immunologic complications of chronic renal failure are associated with the overproduction of proinflammatory cytokines by monocytes. This is partly due to renal failure itself but is further enhanced by hemodialysis treatment with frequent contact between blood and dialyzer membranes. Previous studies have shown an imbalance of proinflammatory and regulatory monokines in these patients. This study examines monokine production in hemodialysis patients using for the first time a very sensitive method of cytokine detection at a single-cell level by flow cytometry ("cytoflow technique"). Monocytes were stained intracellularly for the production of interleukin-6 (IL-6) and IL-10 after 20 h of culture with lipopolysaccharide. It was shown that high levels of proinflammatory IL-6 in hemodialysis patients are due to an increased number of monocytes producing this cytokine, while IL-6 synthesis per cell remains unchanged. In contrast, elevated levels of regulatory IL-10 are due to an increased synthesis per cell. This study demonstrates that in healthy subjects there is a population of monocytes producing exclusively IL-10 after 20 h of stimulation by lipopolysaccharide. This distinct population of regulatory monocytes is infrequent in dialysis patients, in whom most of the IL-10-positive monocytes also produce IL-6. These findings indicate that overproduction of proinflammatory factors in dialysis patients is at least in part due to a loss of cytokine-specific differentiation in monocytes.
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PMID:Production of proinflammatory and regulatory monokines in hemodialysis patients shown at a single-cell level. 972 78

Calcitriol modulates in vivoand in vitro cytokine production: A role for intracellular calcium. Background. Several immunomodulatory properties of calcitriol are currently known, however, only little information is available regarding the in vivo and in vitro effects of calcitriol on cytokine production in chronic renal failure. Methods. To study the in vitro effect of calcitriol on lipopolysaccharide (LPS)-induced cytokine production, peripheral blood mononuclear cells (PBMC, 2.5 ml/ml) from 12 chronic dialytic (HD), 15 undialyzed chronic renal failure (CRF) patients and 10 normal subjects (N) were incubated at 37 degrees for 12 hours with 100 ng of LPS (E. coli and P. maltofilia). Increasing doses of calcitriol from 10-10 to 10-9 M were added and cell associated TNF-alpha and IL-1beta were determined by immunoreactive tests after three freeze-thaw cycles. The intradialytic TNF-alpha and IL-1beta production were evaluated in vivo in 12 HD patients before and after three months of intravenous calcitriol treatment (6 microgram/week). Intracellular calcium [Ca++]i was determined on PBMC with a cytofluorimetric assay using FLUO-3 AM as the indicator. Results. In vitro, TNF-alpha increased from 3.6 +/- 1.9 pg/cell to 1797 +/- 337 in N, from 4.5 +/- 1.7 to 1724 +/- 232 in CRF and from 3.4 +/- 2.3 to 1244 +/- 553 in HD after the LPS stimulus. The production of TNF-alpha was inhibited by calcitriol in a dose-dependent manner [LPS + Vit.D3 100 ng, 2.9 +/- 2.1 in N, 3.7 +/- 1.9 in CRF and 3.4 +/- 1.7 in HD; LPS + Vit.D3 50 ng, 263 +/- 296 (N), 6.73 +/- 11 (CRF), 38 +/- 28 (HD); LPS + Vit.D3 25 ng = 873 +/- 583 (N), 325 +/- 483 (CRF), 588 +/- 507 (HD); LPS + Vit.D3 12.5 ng, 954 +/- 483 (N), 912 +/- 510 (CRF), 875 +/- 527 (HD)]. Comparable data were observed on IL-1beta production. In vivo, the intradialytic TNF-alpha increase (from 8.5 +/- 2.3 to 19 +/- 5.6 pg/2.5 x 106 cell) during hemodialysis was markedly reduced after calcitriol therapy (from 6.6 +/- 3.1 to 11 +/- 4.7). [Ca++]i decreased from 105 +/- 25 to 72 +/- 18 nM (P < 0.05) and a positive correlation between cytokine levels and [Ca++]i was found (r = 0.79; P < 0.001). Conclusions. The in vitro increase of cell-associated cytokine after LPS challenge was inhibited by calcitriol in a dose-dependent manner. These data suggest a possible in vivo modulatory effect of calcitriol therapy on cytokine production in hemodialysis.
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PMID:Calcitriol modulates in vivo and in vitro cytokine production: a role for intracellular calcium. 984 22

We report a case of well-documented typhoid fever in a 30-year-old woman with inactive systemic lupus erythematosus with asymptomatic lupus anticoagulant and high-titer anticardiolipin antibody (aCL). Despite prompt eradication of the Salmonella typhi obtained with appropriate antibiotic therapy, multiple organ system dysfunction occurred. The central nervous system was involved, with ischemic infarcts in the occipital lobes. High-dose corticosteroid therapy failed to improve the neurologic manifestations, which responded to repeated plasmapheresis. A sharp fall in aCL and anti-beta2-glycoprotein I antibody titers was recorded before the start of plasmapheresis. At the same time, IgM and IgG antibodies to Salmonella group O:9 lipopolysaccharide became detectable; the IgM antibodies disappeared within 4 months, whereas the IgG antibodies remained detectable during the next 13 months. Despite treatment with high-dose corticosteroids and cyclophosphamide, rapidly progressive glomerulonephritis developed, leading to chronic renal failure. There is convincing evidence of a link between the S. typhi infection and the ensuing catastrophic syndrome in this patient, probably precipitated by bacterial antigens.
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PMID:Systemic lupus erythematosus-associated catastrophic antiphospholipid syndrome occurring after typhoid fever: a possible role of Salmonella lipopolysaccharide in the occurrence of diffuse vasculopathy-coagulopathy. 1032 64

This paper is a review of three topics related to bio-trace metals. First, the transfer of metals into tissues of patients with chronic diseases treated with hemodialysis is examined. Such diseases include chronic hepatitis, diabetes, and chronic renal failure. In these diseases, metal contents from fingernails were flexible but non-specific. Toxicity may appear as the amount of heavy metals in tissues of patients with chronic renal failure treated with hemodialysis. For example, cadmium and lead were not excreted from the blood of patients during the hemodialysis treatment, and, therefore, their amounts gradually increased in the blood of patients. The level of zinc increased and was excreted in the urine of diabetic patients and experimental animals. Calcium accumulated in the kidney of streptozotocin (STZ)-induced diabetic rats that were fed low zinc diets; and, as a result, severe renal failure occurred. From these results, complication syndromes of either metal deficiency or excesses may occur in tissues of patients with chronic diseases. Second, the role of metallothionein (MT), an inducible protein, and the properties of MT isoforms have been studied on experimental animals. In the exocrine cells of the pancreas, MT was induced by various stresses such as zinc, STZ, alloxan and 4-aminopyrazolo-(3,4-d) pyrimidine, but the effects of those stresses were not clear in the endocrine cells. Therefore, MT may have a role in the exocrine cells of the pancreas. In addition, we were able to separate completely MT-1 and MT-2 isoforms in cytosol fractions of tissues using a capillary zone electrophoresis system at neutral pH without any detergents. Each role of the MT isoforms in the tissues soon started to become clear. Third, cisplatin, a platinum-containing anti-tumor drug, did not penetrate into the brain tissue under physiological conditions, as there is a blood-brain barrier to cerebral tissues; however, it did penetrate with either short-term hypoxia or in the case of lipopolysaccharide-treated experimental animals. Nitric oxide, prostaglandin, and free radicals are related to the penetration. Older rats had a higher sensitivity to cisplatin than younger rats.
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PMID:[Studies of metals and metallothionein in tissue]. 1072 70

Patients with chronic renal failure show an immunodeficiency characterized by frequent infectious complications and a low response to vaccinations. This is paralleled in vitro by a low T-cell proliferation on mitogenic stimuli because of an impaired costimulation by accessory cells. Furthermore, alterations of the cytokine profile are correlated with impaired immune function. The immune system is influenced by both uremia and renal replacement therapy. To evaluate the influence of hemodialysis on immune parameters, we studied patients before and after the initiation of chronic hemodialysis therapy. Fourteen patients with end-stage renal failure were tested before dialysis initiation and during the first 6 weeks of hemodialysis treatment. We determined the in vitro T-cell proliferation, as well as plasma levels of interleukin-6 (IL-6) and the release of IL-6 and IL-10 into culture supernatant poststimulation with lipopolysaccharide. After 6 weeks of intermittent hemodialysis, in vitro T-cell proliferation on stimulation improved significantly (stimulation index, 21.6 +/- 18.5 versus 58.1 +/- 45.5; P < 0.01). This improvement occurred regardless of whether synthetic dialyzers or cellulosic membranes were used for the initiation of dialysis. Plasma IL-6 levels, as well as IL-6 and IL-10 secretion, did not change during the study period. In patients with end-stage renal disease, the initiation of hemodialysis led to a significant improvement of in vitro T-cell proliferation. This effect may have a role for an improvement of immune function in vivo. The expected normalization of IL-6 and IL-10 production may be masked by cytokine induction through hemodialysis membranes.
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PMID:Initiation of hemodialysis treatment leads to improvement of T-cell activation in patients with end-stage renal disease. 1073 80


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