Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to follow the effect of haemodialysis on monocyte function, we measured the release of interleukin-1 beta (Il-1), interleukin-6 (Il-6), and tumour necrosis factor alpha (TNF alpha) from cultured monocytes isolated before and after dialysis. Monocytes obtained from patients before dialysis released smaller amounts of cytokines than cells from healthy controls. The choice of the dialysis membrane had no effect on predialytic monocyte activity. Basal cytokine release after dialysis remained virtually unchanged, irrespective of the membrane material used. When stimulated with LPS, cells significantly produced more cytokines than under basal conditions. Stimulated monocytes isolated before dialysis produced considerably more cytokines than cells obtained at the end of the dialysis. Taken together, uraemia by itself seemed to depress monocyte activity. Haemodialysis either with cuprophan or PMMA dialysers had no influence on basal cytokine release during a 24-h period following dialysis. Uraemic monocytes, however, appeared to be primed, since stimulation with LPS in vitro caused a more pronounced release of cytokines than in healthy volunteers.
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PMID:Cytokine production by monocytes during haemodialysis. 186 62

Phagocytosis is the process where specific cells, phagocytes, ingest foreign material, include it in a cytoplasmatic vacuole, called phagosome, and destroy it. The function of phagocytosis in the immune response has been underevaluated for a very long time. Phagocytosis however, appears to be more and more important in our defense against infection and cancer. The uremic patient presents a well known and increased tendency for infectious disease as well as an increased incidence of cancer. Modern methodology for investigation of phagocytic function consists of: 1. measuring the respiratory burst during phagocytosis; by examining the radio-active CO2 production during the glucose metabolization of phagocytosis. 2. During the chemical reaction of the respiratory burst light is produced. This chemiluminescence can be measured in a Lumetron. In uremia the registration of that chemiluminescence can however be disturbed by the presence of uremic toxins, acting as scavengers of free radicals. 3. Measurement of interleukin-1, interleukin-6 or tumor necrosis factor production during phagocytosis. In the present study, we investigated glucose metabolization and radioactive CO2 production without stimulation and after a challenge with Latex, Zymosan or Staphylococcus Aureus. All tests have been performed on 50 microliter whole blood samples. The following uremic situations have been investigated: 1. Several degrees of increasing renal failure. 2. First weeks of hemodialysis maintenance treatment. 3. Hemodialysis session. 4. Course of hemodialysis maintenance treatment. 5. Continuous ambulatory peritoneal dialysis (CAPD) and renal transplantation. 6. Changes after chemical stimulation by a cephalosporin (cefodizime (R)). The Authors report their detailed results of these investigations and conclude as follows: --uremia is a prototype of acquired immune deficiency. --Contact with bio-incompatible membranes during hemodialysis is disastrous for phagocytosis. --Other toxins than the classical urea or creatinine are apparently responsible for the phagocytic disturbances. --Stimulations of phagocytosis with medication such as the cephalosporin, Cefodizime(R) (Hoechst) is possible.
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PMID:[Phagocyte function in uremic patients]. 192 26

In a previous study, we demonstrated the presence of circulating interleukin-1 (IL-1) in long-term dialyzed patients and that of tumor necrosis factor alpha (TNF alpha) in both long-term and not yet dialyzed uremic patients. In the present study, we attempted to determine the respective influence of hemodialysis (HD) and uremia on the plasma level of interleukin-6 (IL-6), which shares several biological properties with IL-1 and TNF alpha, including the induction of the acute phase response of the inflammatory process. Forty-eight patients with end-stage renal failure, including 32 long-term HD patients and 16 chronic uremic patients undergoing their first dialysis session, were tested for plasma IL-6 using both biological and immunoreactive assays. Plasma IL-6 activity was significantly increased in patients with chronic renal failure (P less than 0.001) compared to its level in normal individuals. No difference was observed, however, between long-term and not yet dialyzed patients. In the patients with the most pronounced IL-6 activity, immunoreactive IL-6 levels between 60 and 150 pg/ml were detected. A monoclonal antibody (mAb) against human IL-6 inhibited the activity of plasma in the IL-6 bioassay, and a close correlation existed between the biological activity of IL-6 and its immunoreactive level. No change in plasma IL-6 was detected during the course of the first dialysis as well as subsequent sessions. Likewise, no influence of the nature (cellulosic or synthetic polyacrilonitrile) of the dialysis membrane equipping the dialyzer was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elevated circulating levels of interleukin-6 in patients with chronic renal failure. 206 12

Immunocompetent cells communicate via direct cellular contact and/or by the release and binding of soluble mediators. These soluble mediators transmit signals for growth and differentiation of various cell types. We have been intensively studying the regulation of human B lymphocytes and have focused on the events which occur following stimulation of mature, resting B cells with antigen or an antigen equivalent, anti-immunoglobulin antibody. Anti-Ig stimulates resting B lymphocytes to enlarge, synthesize RNA, increase membrane Ia expression, express activation markers, and become responsive to soluble factors termed B-cell growth factors (BCGF). We have described two different BCGFs, an 18 kd BCGF derived from a T-T hybridoma and a 60 kd BCGF derived from a T cell line. Activated B cells in the presence of BCGF further enlarge; express another activation marker, the transferrin receptor; and enter the S phase of the cell cycle, but do not differentiate unless another factor is present, e.g., B-cell differentiation factor (BCDF). We have described another T-T hybridoma which constitutively secretes both an 18 kd BCGF and a 35 kd BCDF. These two factors can easily be separated by biochemical means. The 35 kd BCDF induces the differentiation of activated but not resting B cells. Besides these B-cell-specific factors, we have studied the immunoregulatory effects of interleukin 1 (IL-1), IL-2, and interferons (alpha and gamma) on human B-cell responses. Interleukin 1 weakly co-stimulates resting B cells when it is present with anti-Ig and enhances the differentiation of activated and proliferating B cells when it is present in culture with BCDF. Interleukin 2 receptors as defined by the monoclonal antibody anti-Tac and radiolabeled IL-2-binding assays are present on in vitro activated B cells. Recombinant IL-2 added to cultures of in vitro activated B cells promotes both B-cell growth and B-cell differentiation into Ig-secreting cells. Finally, interferons appear to have little direct effect on human B-cell function. Major advances in our understanding of the complexities of B-cell activation, proliferation, and differentiation have been realized over the past few years. The eventual isolation and chemical characterization of the soluble mediators of B-cell function and the receptors for these mediators should lead to further insights and to new approaches to those diseases characterized by aberrations of B-cell function.
Uremia Invest
PMID:Activation and immunoregulation of human B lymphocytes. 608 41

Hyaluronan (HA) is a polysaccharide that forms a critical component of extracellular matrixes. It is present in high concentrations in tissues undergoing remodeling and morphogenesis. Serum HA is elevated in patients with chronic liver disease, and this has been considered to be caused by impaired degradation by the liver endothelial cells. We studied the level of HA in the ascitic fluid and plasma from 27 patients with cirrhotic ascites. These values were compared with peritoneal dialysate effluent (PDE) and plasma from 33 patients with uremia who were undergoing continuous ambulatory peritoneal dialysis (CAPD). The median HA levels in ascitic fluid and plasma from our 26 patients with cirrhosis were significantly higher than corresponding PDE and plasma values from the 33 CAPD patients (p < 0.0001). The median peritoneal/plasma ratios of creatinine, albumin, and immunoglobulin G in either cirrhotic or CAPD patients were less than unity. In contrast, the median peritoneal/plasma ratios of HA in both groups of patients exceeded one with a higher peritoneal/plasma ratio of HA in patients with cirrhosis (p = 0.0035). A significant correlation was observed between the ascitic level of HA and interleukin-1beta, interleukin-6, or transforming growth factor-beta. Our in vitro cell culture studies revealed that HA is synthesized by both mesothelial cells and macrophages. We observed an additive effect in the synthesis of HA by mesothelial cells when the macrophage-conditioned medium was added to the RPMI culture medium. We conclude that a high level of HA is found in ascites from patients with cirrhosis. Our results strongly suggest that simultaneous increased synthesis of HA by the peritoneal cells and a reduction of degradation by liver endothelial cells occur in these patients with cirrhosis with ascites. This event of increased HA synthesis may be contributory to remodeling and regeneration of the peritoneal lining.
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PMID:Increased ascitic level of hyaluronan in liver cirrhosis. 957 89

Bacterial contamination of dialysate may enhance cytokine production in hemodialysis. The authors tested the hypothesis that C-reactive protein and interleukin-6 (IL-6) may be linked in a large group of patients exposed to backfiltration of dialysate over a long period of observation. Plasmas stored in a recently published multicenter study were reevaluated. Plasma C-reactive protein and IL-6 concentrations in patients with chronic uremia undergoing hemodiafiltration, which is known to be associated with backfiltration (Group II, 12 patients), were compared with those found in patients treated with a modified hemodiafiltration modality without backfiltration (Group I, 16 patients), and in patients shifted from one modality to the other (Group III, 27 patients), and in 10 patients on hemodialysis (Group IV) in a 1 year multicenter study. Plasma C-reactive and IL-6 both increased significantly (p < 0.002), but slowly (after 8 months) in Group II compared with I, and during the 4 month period in hemodiafiltration with backfiltration in Group III. Backfiltration of dialysate with a moderate to low degree of contamination may enhance synthesis of cytokine and C-reactive protein in the long term. Thus, the relevance for dialytic strategies aiming at improving dialysate quality or at reducing backfiltration is highlighted.
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PMID:Plasma C-reactive protein is linked to backfiltration associated interleukin-6 production. 980 63

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

Cardiovascular pathology is the major cause of death in uraemia. There is evidence that a chronic inflammation with activation of C-reactive protein, interleukin-6, tumour necrosis factor-alpha and other cytokines is associated with vascular pathology, both in the general population and in dialysis patients. The cardiovascular system, and particularly the vascular wall, is the main target of the inflammatory process. Inflammation of the coronary arteries could be involved in the development of atherosclerosis and its related clinical syndromes. In the uraemic state, an increased production of pro-inflammatory cytokines may trigger the onset and progression of atherosclerosis and favour the subsequent complications, such as plaque fissuration and rupture. However, inflammatory cytokines also have a depressant action on the myocardium, thus inducing myocardial dysfunction. Together, these conditions may ultimately enhance the risk of myocardial infarction and death. From this standpoint, cardiovascular disease should also be investigated with the traditional biochemical inflammation markers and the evaluation of the circulating cytokine level, although new reliable markers could provide further diagnostic help. New therapeutic approaches should also be considered.
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PMID:Cardiac effects of chronic inflammation in dialysis patients. 1214 71

Metabolic and nutritional derangements are prominent features of the uremic syndrome. Recent evidence suggest that several large-molecular-weight molecules that often are elevated in uremia, such as leptin, ghrelin, and proinflammatory cytokines, may have nutritional impact in this patient group. On the basis of present knowledge, these compounds could be regarded as suspected but not established uremic toxins. The discovery of the ob gene, its product leptin, and cerebral leptin receptors has undoubtedly widened our understanding of obesity and the underlying molecular and physiologic mechanisms that regulate food intake and body weight. Moreover, the recent discovery of leptin receptor isoforms in several peripheral organs suggests that leptin besides having a central function also has several important peripheral biological functions. Because uremic patients in general have an inappropriate elevation of circulatory leptin, further research is necessary to determine the potential biological effects of elevated leptin levels in end-stage renal disease. Also, because many symptoms and findings prevalent in the uremic syndrome are known to be associated with elevated levels of proinflammatory cytokines, such as interleukin-6, future studies are needed to evaluate the role of specific anti-inflammatory treatment strategies in malnourished uremic patients.
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PMID:Leptin, ghrelin, and proinflammatory cytokines: compounds with nutritional impact in chronic kidney disease? 1468 62

Protein-energy malnutrition (PEM) and inflammation are common in patients with chronic kidney disease (CKD) and worsen as the CKD progresses toward the end-stage renal disease (ESRD). These conditions are major predictors of poor clinical outcome in kidney failure, as reflected by a strong association between hypoalbuminemia and cardiovascular disease (CVD). It has been suggested that inflammation is the cause of both PEM and CVD and, hence, the main link among these conditions, but these hypotheses are not well established. Increased release or activation of inflammatory cytokines, such as interleukin-6 or tumor necrosis factor alpha, may suppress appetite, cause muscle proteolysis and hypoalbuminemia, and may be involved in atherogenesis. Increasing serum levels of proinflammatory cytokines caused by reduced renal function, volume overload, oxidative or carbonyl stress, decreased levels of antioxidants, increased susceptibility to infection in uremia, and the presence of comorbid conditions may lead to inflammation in CKD patients. In hemodialysis patients, the exposure to dialysis tubing and dialysis membranes, poor quality of dialysis water, back-filtration or back-diffusion of contaminants, and foreign bodies in dialysis access maybe additional causes of inflammation. Similarly, episodes of overt or latent peritonitis, peritoneal dialysis (PD) catheter and its related infections, and constant exposure to PD solution may contribute to inflammation in these patients. The degree to which PEM in dialysis patients is caused by inflammation is not clear. Because both PEM and inflammation are strongly associated with each other and can change many nutritional measures and outcome concurrently in the same direction, the terms malnutrition-inflammation complex syndrome (MICS) and/or malnutrition-inflammation-atherosclerosis (MIA) have been suggested to denote the important contribution of both of these conditions to poor clinical outcome. Maintenance dialysis patients who are underweight or who have low serum levels of cholesterol, creatinine, or homocysteine may be suffering from the MICS/MIA and its subsequent poor outcome. Consequently, obesity and hypercholesterolemia may appear protective, which is known as reverse epidemiology. Although MICS/MIA may have a significant contribution in reversing the traditional CVD risk factors in dialysis patients, it is not clear whether PEM or inflammation and their complications can be effectively managed in CKD and ESRD or whether their management improves clinical outcome.
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PMID:Inflammation and nutrition in renal insufficiency. 1470 70


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