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

Patients with alcoholic liver cirrhosis (ALC) have high serum levels and spontaneous in vitro production of immunoglobulin (Ig) A. Deposits of IgA are also found in liver sinusoids. Increased interleukin 6 (IL-6) production is another feature of this disease. This study shows a linear correlation between increased lipopolysaccharide (LPS)-induced IL-6 production and increased spontaneous IgA and IgG secretion by peripheral blood mononuclear cells (PBMCs). PBMCs and purified monocytes isolated from healthy control subjects and patients with ALC contain elevated IL-6 messenger RNA levels and produce IL-6 in response to stimulation with soluble polymeric IgA (p-IgA) or attached monomeric IgA (m-IgA) but not with soluble m-IgA. The addition of monospecific antibody to human IL-6 inhibits spontaneous IgA production by PBMC. This inhibition is more pronounced in patients with ALC. These data provide evidence that IgA, possibly by attachment to cells possessing Fc alpha receptors and secreting IL-6, is involved in the production of this major mediator and the amplification of Ig secretion. Circulating IgA and IgA deposits could therefore initiate a process of autoamplification implicated in the development of hypergammaglobulinemia in ALC.
 ...
PMID:Immunoglobulin A and interleukin 6 form a positive secretory feedback loop: a study of normal subjects and alcoholic cirrhotics. 139 88

The in vitro production of the acute-phase mediator interleukin-6 by peripheral blood monocytes derived from patients with various liver diseases was studied. Compared with healthy controls (n = 45; 860 +/- 92 U/ml, mean +/- SEM), monocytes from patients with chronic hepatitis B produced significantly lower amounts of interleukin-6 (n = 14; 424 +/- 126 U/ml) after stimulation with lipopolysaccharide (p = 0.02), whereas monocytes from patients with chronic hepatitis non-A, non-B secreted normal amounts of interleukin-6 (n = 13; 672 +/- 151 U/ml; n.s.). In contrast, monocytes of patients suffering from alcoholic liver cirrhosis (n = 22; 1310 +/- 153 U/ml) or primary biliary cirrhosis (n = 6; 1450 +/- 186 U/ml) produced higher amounts of interleukin-6 than healthy control individuals (p = 0.03, respectively). Lipopolysaccharide-stimulated monocytes derived from patients with acute hepatitis A, B and non-A, non-B showed an interleukin-6 production not different from that seen in healthy control individuals and did not experience a discernible change during the course of the acute disease. These results suggest that the production of the acute-phase mediator interleukin-6 varies in chronic liver disease in accordance with various etiologies with a reduced lipopolysaccharide-inducible interleukin-6 response in chronic hepatitis B and an enhanced response in alcoholic liver cirrhosis and primary biliary cirrhosis.
 ...
PMID:Interleukin-6 production by peripheral blood monocytes in patients with chronic liver disease and acute viral hepatitis. 144 5

Interleukin-1 (IL-1) is a cytokine produced by the macrophage-monocyte system that has important effects on immunological responses and inflammatory reactions. Several clinical studies have shown that severe protein energy malnutrition adversely effects cell-mediated immune responses and the functional state of macrophages. The objective of this study was to analyse IL-1 production by adherent cells stimulated in vitro with lipopolysaccharide B (LPS) from patients with alcoholic cirrhosis of the liver and its possible relationship with nutritional states. Forty-five patients with alcoholic cirrhosis and 28 healthy donors were investigated. A combined index of nine anthropometric and biochemical parameters was used to evaluate nutritional status of cirrhotic patients, allowing a distinction to be made between those patients with acceptable nutrition (group I: 40%), those with slight malnutrition (group II: 37.7%), and those with severe malnutrition (group III: 22.3%). IL-1 activity was significantly lower in the cirrhosis patients than in the controls (P less than 0.001). This activity also was significantly lower in samples obtained from cirrhotics with severe malnutrition than in those with acceptable nutrition (P less than 0.05); the combined index and the sole anthropometric index gave the same results, suggesting that malnutrition may play a role in the immunoregulatory disturbances in the pathogenesis of alcoholic liver disease.
 ...
PMID:Interleukin-1 in alcoholic cirrhosis of the liver: the influence of nutrition. 162 57

Under endotoxin-free conditions, peripheral blood mononuclear cells and purified monocytes isolated from healthy control subjects and patients with alcoholic cirrhosis disclose elevated tumor necrosis factor alpha messenger RNA level and produce tumor necrosis factor alpha in response to stimulation by either soluble polymeric IgA or monomeric IgA bound to the surface of culture dishes but not by soluble monomeric IgA. Polymeric IgA induces tumor necrosis factor alpha secretion in a dose-dependent fashion. These results suggest that cross-linking of Fc alpha receptors on human monocytes induces the messenger RNA accumulation and the secretion of the cytotoxic and immunoregulatory cytokine tumor necrosis factor alpha. Furthermore, it is shown that lipopolysaccharide-induced tumor necrosis factor alpha secretion by peripheral blood mononuclear cells is synergistically enhanced in the presence of solid phase monomeric IgA but not in the presence of either soluble monomeric or polymeric IgA. Although increased lipopolysaccharide-induced tumor necrosis factor alpha secretion is observed at baseline in alcoholic cirrhotic patients, this synergism is also expressed in this group of patients. These observations could be of pathophysiological relevance in alcoholic cirrhosis because monomeric IgA deposits along the liver sinusoids and increased serum levels of polymeric IgA are common even in the early stages of this disease.
 ...
PMID:IgA triggers tumor necrosis factor alpha secretion by monocytes: a study in normal subjects and patients with alcoholic cirrhosis. 201 Jan 62

The objective of this study was to analyze monokine production by peripheral blood mononuclear cells from patients with alcoholic cirrhosis. The capacity of peripheral blood mononuclear cells and purified monocytes from these patients to produce tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 was investigated. Spontaneous production of tumor necrosis factor alpha, interleukin 6 and interleukin 1 beta was similar in cirrhotic and healthy subjects, but serum levels of interleukin 6 (less than 2 U/ml vs. 9.5 +/- 3 U/ml) and tumor necrosis factor alpha (3.1 +/- 1.2 pg/ml vs. 12.0 +/- 1.2 pg/ml) were significantly higher in cirrhotic patients. However, peripheral blood mononuclear cells or purified monocytes from patients with alcoholic liver cirrhosis, stimulated in vitro with Escherichia coli lipopolysaccharide, displayed a marked increase of tumor necrosis factor alpha, interleukin 1 beta and interleukin 6 secretions compared with healthy controls. A striking feature of this overproduction was its reversibility as assessed by allowing cells to rest in vitro without lipopolysaccharide for 1 to 7 days before stimulation. In such conditions, tumor necrosis factor alpha and interleukin 6 secretions declined to levels present in healthy subjects in whom production remained stable, whereas interleukin 1 beta secretion markedly decreased in both groups to the point where no difference could be seen. This reversible oversecretion of cytokines after lipopolysaccharide stimulation, along with the lack of abnormality of spontaneous cytokine secretion, suggests that monocytes in these patients may have undergone an in vivo activation process analogous to a priming phenomenon. The in vitro activation with lipopolysaccharide may represent the correlate of in vivo endotoxemia observed during acute events such as sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Excessive in vitro bacterial lipopolysaccharide-induced production of monokines in cirrhosis. 218 15

Interleukin-1 and tumor necrosis factor-alpha activity by E. coli lipopolysaccharide-triggered monocytes were studied in patients with chronic alcoholic liver disease. Monocytes from cirrhotic patients were shown to have a significant reduction in IL-1 and TNF-a activity, compared with that from age- and sex-matched healthy controls. These findings indicate further immunoregulatory disturbances concerning alcoholic liver cirrhosis.
 ...
PMID:Depressed monocyte production of interleukin-1 and tumor necrosis factor-alpha in patients with alcoholic liver cirrhosis. 258 42

Interleukin-1 and tumour necrosis factor-alpha activities by E. coli lipopolysaccharide-triggered monocytes were studied in patients with chronic alcoholic liver disease. Monocytes from cirrhotic patients were shown to have significantly reduced IL-1 and TNF-a activities, compared with that from age and sex matched healthy controls. These findings indicate further immunoregulatory disturbances concerning alcoholic liver cirrhosis.
 ...
PMID:Studies on the monocyte interleukin-1 and tumour necrosis factor-alpha production in patients with alcoholic liver cirrhosis. 263 61

In alcoholic cirrhosis, high levels of serum IgA make a prominent contribution to hyperglobulinaemia. Kinetic studies indicate that this predominantly reflects enhanced IgA synthesis rather than catabolism. Increase IgA synthesis might reflect increased antigenic load, diminished T-cell suppression, or T-cell independent B-cell stimulation (for example by lipopolysaccharide). To investigate this we studied T-cell control of IgA production by peripheral blood cells. Six patients with alcoholic cirrhosis were compared with six normal individuals. Serum IgA levels were significantly higher in the patients (6.6 mg/ml, SD 2.8 cf 1.7 mg/ml, SD 1.2). Seven day unstimulated cultures of peripheral blood mononuclear cells yielded supernatant IgA concentrations of 1,025 ng/ml (SD 600) in patients and 363 ng/ml (SD 222) in controls. T-cell control of IgA synthesis was explored by rosetting out T-cells, and reconstituting cultures at varying T:non-T cell ratios. Similarly shaped curves relating IgA per million non-T cells to the T:non-T cell ratio were found, with maximum IgA production at a T:non-T ratio of 8:2 in each group. IgA production at this ratio was 6.4 micrograms/ml/million non-T cells (SD 3.2) in cirrhosis of 3.2 (SD 1.0) in controls. T-cell control of IgA production thus appears normal, though set at a higher level, implying enhanced T-cell independent drive to IgA production in alcoholic cirrhosis.
 ...
PMID:Regulation of peripheral blood B-cell IgA production in alcoholic cirrhosis. 264 70

Gram-negative bacterial infections are frequent and severe in cirrhotic patients. Existence of endotoxemia in cirrhosis is controversial. The demonstration of Gram-negative bacterial antibodies could be an alternative approach to the pathogenic role of these bacteria. In 58 patients with alcoholic cirrhosis, the immunoglobulin G specifically directed against the Gram-negative bacteria lipopolysaccharide expressed by the J5 mutant of Escherichia coli 0111:B4 was measured. Antibody titres were compared to those of a control group of blood donors. The distributions of antibody titres were similar in cirrhotic patients and in control subjects. No correlation was found between antibody titres and biological parameters of liver function. These results seem to confirm previous reports on the absence of latent endotoxemia in cirrhotic patients, and they suggest that antibody production against Gram-negative bacteria lipopolysaccharides is not enhanced in these patients.
 ...
PMID:[Anti-Gram-negative bacterial antibodies in alcoholic cirrhosis. Study of 58 patients]. 674 68

An enzyme-linked immunosorbent assay was used to detect antibody to specific bacterial lipopolysaccharide (LPS) in serum and in pokeweed mitogen (PWM) stimulated culture supernatants of peripheral blood mononuclear cells from four patients with alcoholic cirrhosis (AC). Antibody to LPS (derived from a single strain of Escherichia coli isolated from each patient's stool), was detected in the sera of each patient to a 10(-4) dilution. Only one of four control sera was positive at the 10(-4) dilution, with the others positive at 10(-3) dilution. Antibody to LPS was detected in the culture supernatants in three of the four patients and in none of the control subjects. Supernatants from patient cultures pretreated with mitomycin C or harvested after 1 day of incubation did not have detectable antibody. These results indicate that we can expand, in vitro, the population of peripheral blood B lymphocytes obtained from patients with AC and cause them to synthesize antibody against specific LPS from their own gut flora.
 ...
PMID:In vitro synthesis of antibody to specific bacterial lipopolysaccharide by peripheral blood mononuclear cells from patients with alcoholic cirrhosis. 701 48


1 2 3 Next >>