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 determine the influence of dialysis membranes on immunoglobulin (Ig) and interleukin-6 (IL-6) production, peripheral blood mononuclear cells (PBMC) from 11 haemodialysis patients were cultured for 7 days on Cuprophan, Hemophan, and polyacrylonitrile flat-sheet dialysis membranes. IL-6, IgG, IgA, and IgM were assayed in the supernatants using ELISA. Pokeweed-mitogen-stimulated IgG production declined significantly from 319 +/- 40 ng/ml on polystyrole to 162 +/- 26 ng/ml on Cuprophan, 135 +/- 25 ng/ml on Hemophan, and 109 +/- 20 ng/ml on polyacrylonitrile. A similar pattern was observed for IgA production by PBMC. In comparison to polystyrole (724 +/- 34 pg/ml), IL-6 production by PBMC was significantly reduced in the presence of Cuprophan (151 +/- 45 pg/ml), Hemophan (167 +/- 6 pg/ml) and polyacrylonitrile (108 +/- 33 pg/ml). The fact that the level of monocyte-derived IL-6, a stimulator of B cells, was decreased suggests that reduced B cell activity may be due to diminished stimulation by monocytes.
Nephrol Dial Transplant 1991
PMID:Dialysis membranes decrease immunoglobulin and interleukin-6 production by peripheral blood mononuclear cells in vitro. 177 66

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.
Nephrol Dial Transplant 1991
PMID:Cytokine production by monocytes during haemodialysis. 186 62

Our aim was to evaluate the role of three different variables in the activation of the monocyte system: dialysis membrane (cuprophane or polyacrylonitrile), dialysate (acetate or bicarbonate), and procedure (standard or high-flux haemodialysis). By ELISA test we measured the 'in vivo' intracellular (monocyte-associated) production and extracellular release of tumour necrosis factor alpha (TNF alpha), interleukin-6 (Il-6) and beta 2-microglobulin (beta 2-M) by monocytes from 20 uraemic patients before and after the dialysis session. At the beginning of the dialysis session, uraemic patients' cultured monocytes spontaneously released a greater amount of TNF alpha, Il-6 and beta 2-M compared to normal controls. However, no differences in cytokine and beta 2-M were observed in monocyte lysate between the two groups. At the end of the dialysis session, cultured monocytes from patients treated with cellulosic membranes and acetate dialysate showed greater TNF alpha values than normal controls (P less than 0.001 and P less than 0.05 respectively). Moreover, TNF alpha and Il-6 values were strictly correlated (P less than 0.05). These results clearly show an activation of the monocyte system in uraemic patients undergoing periodic haemodialysis. The implicated factors may be multiple, such as complement activating cellulosic membranes or acetate dialysate. The production of TNF alpha, Il-6 and beta 2-M may explain some of the pathological findings observed in long-term haemodialysis patients.
Nephrol Dial Transplant 1991
PMID:Involvement of peripheral blood monocytes in haemodialysis: in vivo induction of tumour necrosis factor alpha, interleukin 6 and beta 2-microglobulin. 186 63

Interleukin-6 (Il-6) has a complex spectrum of biological activities (growth and differentiation of B cells and synthesis of acute-phase proteins by liver). To evaluate the role of this cytokine in the inflammatory response induced by blood interaction with haemodialysis membranes, we have investigated Il-6 synthesis and release in supernatant of 24-h cultured peripheral blood mononuclear cells (PBMC) isolated from ten haemodialysed patients and eight healthy control subjects. In haemodialysed patients, blood samples were drawn before and after their usual dialytic treatment with cuprophane membranes and following 1 and 2 months with polymethylmethacrylate (PMMA) membranes. Il-6 was determined by 72-h incubation of serial dilutions of PBMC supernatant with Il-6-dependent cell line 7TD1; dilutions of rIl-6 were included as standard. Compared to Il-6 synthesis in control subjects (3.3 +/- 2.8 U/ml) the patients usually haemodialysed with cuprophane membranes showed significantly greater values (9.8 +/- 4.5 U/ml, P less than 0.02 before the treatment, and 10.4 +/- 6.1 U/ml, P less than 0.05 after the treatment). A significant reduction, in comparison with the values obtained with cuprophane membranes, was obtained after 1 month (5.3 +/- 2 U/ml, P less than 0.02 before the treatment, and 7.5 +/- 6 U/ml after the treatment) and especially after 2 months (3.4 +/- 3.2 U/ml, P less than 0.02 before the treatment, and 4.4 +/- 3.4 U/ml, P less than 0.05 after the treatment) of dialysis with PMMA membranes. In conclusion, our results show increased Il-6 production in haemodialysed patients usually treated with cuprophane membranes, suggesting a chronic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1991
PMID:Interleukin-6 production of uraemic haemodialysed patients: effects of different membranes. 186 79

Mesothelial cells that line the peritoneal cavity are capable of producing several proinflammatory cytokines such as interleukin-6 and interleukin-8. Since they are the most numerous cell in the peritoneal cavity when the lining mesothelial cells are included, they may play a major role in the local antibacterial defence mechanism. Cancer antigen (CA)125 is expressed by mesothelial cells (as by other coelomic epithelium-derived cells) and might therefore be considered a marker of the mesothelium. The aim of this study was to determine whether CA125 is a bulk or an activation stage mesothelial cell marker. A positive correlation was found between the mesothelial cell number and the CA125 concentration in dialysate of stable PD patients (P = 0.03). CA125 release by mesothelial cell cultures during confluence showed that the release per cell was constant in time. Stimulation of mesothelial cells in a confluential phase with IL1 beta, TNF alpha, IFN gamma and TGF beta did not result in an increase in CA125 release. Cell lysis showed that CA125 is also present intracellularly. This implies that release of intracellular CA125 can be a disturbing factor in interpreting the CA125 concentration of dialysate in situations where mesothelial cell death may occur, such as in peritonitis. It can be concluded, that our data show that dialysate CA125 is a bulk marker for the mesothelial cell mass in stable PD patients and can thus provide data on the state of the peritoneal membrane in the follow-up of the individual patient.
Nephrol Dial Transplant 1995
PMID:Cancer antigen 125: a bulk marker for the mesothelial mass in stable peritoneal dialysis patients. 772 31

Interleukin-6 is involved in T-cell activation and possibly plays a role in the pathogenesis of acute rejection of transplanted organs. This is indicated by elevated levels of interleukin-6 in serum and urine of renal allograft recipients, and elevated amounts of mRNA for interleukin-6 in all different cell types of the renal allograft during acute rejection episodes. However, transplant recipients receive immunosuppressive drug therapy which may inhibit production of interleukin-6 at the post-transcriptional level. Therefore, the aim of the present study was to detect interleukin-6 in biopsies taken during acute renal allograft rejection by immunohistochemical staining. In addition, serial sections were stained with cellular markers to identify interleukin-6-producing cells. In biopsies taken during acute rejection (n = 7), interleukin-6 could be detected in tubular cells (7/7) mesangial cells (3/7) and monocytes/macrophages (4/7), but not in vascular endothelium or lymphocytes. In control biopsies weak interleukin-6 staining of tubular cells only was present or there was no staining at all. We conclude that interleukin-6 is actually produced in the renal allograft during acute rejection, and that elevated urinary interleukin-6 levels during acute rejection seem to originate mainly from synthesis of interleukin-6 by renal tubular cells.
Nephrol Dial Transplant 1993
PMID:Local production of interleukin-6 during acute rejection in human renal allografts. 838 42

Erythropoiesis is controlled by different regulators. Interleukin 3, granulocyte-macrophage colony-stimulating factor and stem cell factor play regulatory functions in the early steps of erythropoiesis. Erythropoietin (Epo) is the main factor which acts positively on the last steps of the production of erythrocytes in mammals. Epo is specific for the erythroid progenitor cells and has only little effect on other cells. The target cells for Epo are the erythroid progenitors (BFUe and CFUe). Epo acts on these progenitors through surface receptors specific for Epo. Epo induces the proliferation and differentiation of erythroid progenitors leading finally to reticulocytes. During this process, certain conditions are required to permit this differentiation: progenitors must be present in sufficient numbers, the bone marrow environment must be normal, and nutrients such as folic acid, vitamin B12 and particularly iron must be available. Elemental iron is an absolute requirement for adequate haemoglobin formation. Indeed, in a normal adult, without any stimulation, the bone marrow synthesizes 4 x 10(14) molecules of haemoglobin per second, each molecule containing four atoms of iron, which roughly corresponds to 20 mg iron. On the other hand, erythropoiesis is negatively regulated by several cytokines. These are macrophage-derived cytokines, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta). All these factors are elevated in the inflammatory state and are implicated in the pathogenesis of anaemia of chronic disease. TNF-alpha has an inhibitory effect on erythroid progenitors either directly or mediated by interferon-beta (INF-beta). IL-1 inhibits erythropoiesis in vivo in mice and in vitro in humans.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1995
PMID:Cellular mechanism of resistance to erythropoietin. 852 90

Our objective was to determine the incidence of peritonitis episodes with an impaired initial cell reaction (IICR:neutrophil number < 100 x 10(6)/L) over a period of ten years, and to find possible explanations for this unusual presentation of peritonitis. A retrospective review of the files of continuous ambulatory peritoneal dialysis (CAPD) patients included in the CAPD program 1984 and 1993 was done. Analysis of cytokine and prostanoid patterns during four peritonitis episodes with an IICR was compared to 12 episodes with a normal initial cell reaction (NICR). Dialysate cell numbers and immunoeffector characteristics of peritoneal cells were compared in 7 IICR patients in a stable situation and a control group of 70 stable CAPD patients. The setting was a CAPD unit in the Academic Medical Center in Amsterdam. Thirty-five CAPD patients who had one or more peritonitis episodes with an IICR and a control group of 249 CAPD patients were included in the study. The incidence of peritonitis with an IICR was 6%. These episodes occurred more than once in 51% of the patients who presented with IICR. In 72% the cell reaction was only delayed: a cell number exceeding 100 x 10(6)/L was reached later. Staphylococcus aureus was significantly more frequently the causative microorganism compared to all peritonitis episodes (PE) that occurred during the study period. Patients with IICR had lower dialysate cell counts in a stable situation, compared to a control group (p < 0.01). This was caused by a lower number of macrophages and CD4 positive lymphocytes. The phagocytosis capacity of the macrophages appeared to be normal. In a comparison of four PE with an IICR and 12 episodes with an NICR, the tumor necrosis factor-alpha (TNF-alpha) response was similar and occurred on day 1, also pointing to normally functioning macrophages. However, the maximal appearance rates of interleukin-6 (IL-6) and IL-8 occurred later in the episodes with IICR compared to NICR (day 2 vs day 1, p < 0.05). No differences were found in vasodilating prostaglandins, mesothelial cell markers (cancer antigen 125, phospholipids, hyaluronan), and mesothelial cell numbers in the stable situation nor during peritonitis. Peritonitis can present as abdominal pain in the absence of a cloudy dialysate. In some of the patients this presentation occurred more than once. This impaired, most often delayed, cell reaction was associated with a delayed secondary cytokine response. As IL-6 and IL-8 can be synthesized by mesothelial cells, this suggests an impaired functioning mesothelium. This could not be confirmed, however, by a lower number of mesothelial cells in effluent or lower dialysate levels of mesothelial cell markers.
Perit Dial Int 1996
PMID:Impaired initial cell reaction in CAPD-related peritonitis. 872 24

Advanced glycation end-products (AGEs) are formed in long-lived matrix proteins by a non-enzymatic reaction with sugar. We recently demonstrated the presence of AGEs in amyloid fibrils of dialysis-related amyloidosis, one of the characteristic features of which is an accelerated bone resorption around amyloid deposits. This suggested a potential link of AGEs in bone resorption and led us to investigate whether AGEs enhance bone resorption. An immunohistochemical study using anti-AGE antibody revealed positive immunostaining for AGEs in bone tissues from elderly subjects. AGE-modified proteins were shown to stimulate monocyte/macrophage to secrete bone-resorbing cytokines such as interleukin-1 beta, interleukin-6 and tumour necrosis factor- alpha. AGE-modified proteins enhanced net calcium efflux in cultured neonatal mouse calvariae to a much greater extent than unmodified proteins. Furthermore, when mouse unfractionated bone cells containing osteoclasts were cultured on dentin slices, AGE-modified proteins increased the number of resorption pits formed by osteoclasts, whereas their normal counterparts or those modified with the early glycation products did not. These findings suggest that AGEs enhance bone resorption by osteoclasts. The modification of bone matrices with AGEs might, therefore, play a pathophysiological role not only in the remodelling of senescent bone matrix tissues, but also in dialysis-related amyloidosis or osteoporosis associated with diabetes and ageing.
Nephrol Dial Transplant 1996
PMID:Possible involvement of advanced glycation end-products in bone resorption. 904 8

Recent studies have emphasized the role of peritoneal mesothelial cell (PMC) in peritoneal immune defense mechanisms in continuous ambulatory peritoneal dialysis (CAPD). The aim of this study was to evaluate a possible relationship between peritoneal dialysis effluent (PDE), cytokine (Cy) levels, and PMC viability and their impact on peritonitis morbidity. Fifteen patients initiating CAPD for end-stage renal failure participated in the study. The following parameters were evaluated: (1) the levels of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-6 (IL-6), and interleukin-8 (IL-8) in PDE samples taken 7 days after initiating CAPD, at the end of the first, third, and sixth month of CAPD (determined by a solid phase enzyme amplified sensitivity immunoassay EASIA); (2) peritoneal mesothelial cell viability [determined by the release of lactate dehydrogenase (LDH) and by trypan blue extrusion test] by isolating and culturing peritoneal mesothelial cells at the moment of the placement of the peritoneal catheter and at the sixth month of CAPD; (3) peritonitis incidence during the 24 months after starting CAPD. At the first month of CAPD in all patients there was a slight increase in PDE IL-1 beta and TNF-alpha levels, while other Cy were almost undetectable. Time course studies showed that in 10 patients (Group I) there was a significant increase in PDE levels of IL-6, IL-8, and INF-gamma (p < 0.0005) in comparison to other Cy and a good PMC viability. In the other 5 patients (Group II) there were higher PDE levels of IL-1 beta and TNF-alpha (p < 0.0005). This was associated with a marked reduction in PMC viability determined by the release of LDH and by the trypan blue extrusion test. During the 24 months after starting CAPD, incidence of peritonitis was one episode per 24 patient-months in Group I and one episode per 9.2 patient-months in Group II. Our results show that from the beginning of CAPD there are distinct patterns of Cy in the PDE that correlate with a different PMC viability and peritonitis morbidity. Thus the analysis of the above-mentioned parameters may be useful in the early identification of the risk of peritonitis, thus allowing preventive measures.
Adv Perit Dial 1997
PMID:Peritoneal dialysis effluent, cytokine levels, and peritoneal mesothelial cell viability in CAPD: a possible relationship. 936 Jun 42


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