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)

The mesangial cell occupies a central position in the genesis of the pertubations occurring during the pathogenesis of glomerulonephritis. In vitro studies have shown that this cell is a metabolically active cell producing a variety of cytokines which act as autocoids; such cytokines are also liberated by the monocytes/macrophages which infiltrate the glomerulus in nephritis. This review summarizes the evidence for the participation of these cytokines in animal models of nephritis and in human renal disease, focusing on the roles of basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, colony-stimulating factor-beta, tumor necrosis factor, interleukin-1, and interleukin-6.
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PMID:Biology of the mesangial cell in glomerulonephritis--role of cytokines. 898 6

C57BL/6 human interleukin-6 (IL-6) transgenic mice develop mesangial proliferative glomerulonephritis with massive IgG1 plasmacytosis and die of renal failure in early life. To test whether the IL-6 overexpression could cause development of mesangial proliferative glomerulonephritis without plasmacytosis or promote proliferation of immature B cells that have not undergone immunoglobulin gene rearrangement, the IL-6 transgene was introduced into mice with severe combined immunodeficiency (SCID). In the immunocompetent littermate IL-6 transgenic mice, there were various symptoms such as plasmacytosis, nephropathy, anemia, and thrombocytosis, accompanied by marked increases in serum IL-6 levels as they aged. All these mice died by 25 weeks of age. In contrast, the SCID-IL-6 transgenic mice had no such abnormalities, except certain hematological changes, although the transgene was expressed in various tissues. In these mice, the serum IL-6 levels were 10- to 15-fold higher than those in the nontransgenic mice, and they remained constant throughout their lives. Furthermore, there were no signs of lymphoid development. This study demonstrates that deregulation of IL-6 expression does not stimulate cell growth or differentiation of immature B cells, and thus does not result in plasmacytosis and age-related increases in IL-6 production, and also does not generate mesangial proliferative glomerulonephritis.
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PMID:Interleukin-6 overexpression cannot generate serious disorders in severe combined immunodeficiency mice. 900 Apr 79

The activity of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, is associated with insulin resistance (IR) and the risk of venous and arterial thrombotic cardiovascular disease (CVD) in the general population, and may behave as an acute-phase reactant. PAI-1 activity was measured in 124 patients with chronic renal disease, and its relationship with alterations in metabolic, lipid, and cytokine parameters and the prevalence of CVD complications was explored. Patients with chronic renal disease not requiring dialysis were divided into a low proteinuric ([LP]n = 30) or high proteinuric ([HP]n = 31) group and compared with patients on continuous ambulatory peritoneal dialysis ([CAPD]n = 32) or hemodialysis([HD]n = 31) and with 31 healthy controls. Patients on HD had significantly lower PAI-1 activity than HP, CAPD, and control groups, but no group had significantly higher values than the controls (AU/mL: 7.4 +/- 3.8 HD, 11.2 +/- 8.4 CAPD, 9.4 +/- 5.4 LP, 12.1 +/- 8.0 HP, 11.4 +/- 6.6 controls, P = .04). Interleukin-6 (IL-6), the mediator of the acute-phase response, was determined in a subset of patients and was significantly increased in HD, CAPD, and LP groups compared with the controls (median, pg/mL: 4.6 HD, 4.0 CAPD, 2.9 LP, 2.4 HP, and 1.5 controls, P < .001), but did not correlate with PAI-1. PAI-1 independently correlated with body mass index (BMI), triglycerides, and lipoprotein(a) [Lp(a)] in stepwise regression for all patients. Dividing the whole patient group by tertiles of triglycerides and BMI, increased PAI-1 was confined to the subgroup of patients with both obesity (BMI > 26.7 kg/m2) and hypertriglyceridemia (triglycerides > 2.5 mmol/L). These data suggest that PAI-1 activity in chronic renal disease and dialysis was more strongly associated with the common metabolic abnormalities of obesity and hypertriglyceridemia than with renal disease status, dialysis, or a chronic inflammatory state. This study does not support but does not exclude a major role for increased PAI-1 activity in CVD risk in chronic renal disease.
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PMID:Plasminogen activator inhibitor-1 activity in chronic renal disease and dialysis. 900 66

Serum and urinary tumor necrosis factor-alpha (SeTNF and UTNF) and interleukin-6 (SeIL-6 and UIL-6) by ELISA method were determined in 99 patients with glomerulonephritis (GN): 13 with extracapillaris GN (ExGN), 38 with membranoproliferative GN (MPGN), 33 mesangial proliferative GN (MesPGN), 5 with focal segmental glomerulosclerosis (FSGS), 5 with membranous nephropathy (MN), 3 with minimal change nephropathy (MC) and in 32 healthy adults. The higher levels of Se TNF than those in the healthy were in 25 patients: in nearly all with ExGN, in 8 with MPGN and in single patients with other GN. In all patients with high SeTNF were many extra renal organs involvement. Measurable levels of UTNF were in 30 patients (30%) (in 12 with ExGN, 9 with MPGN, 7 with MesPGN, 1 with MN, and 1 with FSGS). Most patients with high SeTNF belonged to group I. The higher levels of SeIL-6 than those in healthy were in 17 patients belonging to group I, in which high SeIL-6 were in 3 patients with ExGN, 6 with MPGN, 3 with MesPGN, 2 with MN, and 3 with FSGS. Measurable urinary IL-6 levels were in 27 (27%) patients, mainly in group I, and in single patients in other groups. The majority of patients with ExGN and MPGN from group I and UIL-6 positive suffered from renal insufficiency and histologically had proliferative GN. We conclude that the elevation of TNF alpha and/or IL-6 in plasma may reflect a secondary consequence of immune cells activation while urinary TNF alpha and/or IL-6 may be secreted by activated glomerular cells. Thus, high levels of TNF alpha and/or IL-6 in serum of patients with GN and extra renal organs involvement, peculiary with infections, suggested antibiotics therapy, because infection may stimulated cytokines production and they are important in pathogenesis and progress of GN. High urinary levels of IL-6 and (or) TNF alpha in patients with proliferative GN suggest great disease activity and is useful in the evaluating of IS treatment.
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PMID:[Tumor necrosis factor (TNF) and interleukin-6 (IL-6) in patients with glomerulonephritis]. 912 13

Renal infiltration of human immunodeficiency virus type 1 (HIV-1)-infected monocytes might play an important role in the development of HIV-associated nephropathy (HIVAN). In the present study, we investigated the effects of cytokines produced by cultured human mesangial cells (HMC) and proximal tubular epithelial cells (PTEC) on HIV-1 expression in chronically HIV-1-infected promonocytes (U1 cells). Human mesangial cells constitutively secreted interleukin-6 (IL-6) but not tumor necrosis factor-alpha (TNF-alpha) into the culture medium, whereas PTEC constitutively secreted both IL-6 and TNF-alpha. Coculture of U1 cells with HMC or PTEC for 72 hours markedly stimulated HIV-1 expression, with the p24 antigen concentration in the coculture supernatants ranging from approximately 200 to 1850 pg/ml. The presence of anti-IL-6 antibody in the coculture medium nearly completely blocked HIV-1 expression in the HMC/U1 cell cocultures (P < 0.05). Anti-IL-6 antibody and anti-TNF-alpha antibody blocked HIV-1 expression in the PTEC/U1 cell cocultures by 40% and 53%, respectively (P < 0.05). Moreover, the combination of anti-IL-6 and anti-TNF-alpha antibodies additively reduced coculture HIV-1 expression by 87% (P < 0.05). We conclude that renal cell production of IL-6 and TNF-alpha might provide a potent stimulus for HIV-1 expression in HIV-1-infected monocytes that infiltrate the kidney, and that this may play an important role in the pathogenesis of HIVAN.
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PMID:Renal cell cytokine production stimulates HIV-1 expression in chronically HIV-1-infected monocytes. 950 3

In the hope of identifying agents of therapeutic value in immunoglobulin A nephropathy (IgA-N), we tested crude methanol extracts of 15 Chinese herbs for their effect on human mesangial cel proliferation in vitro. The results indicated that 7 out of the 15 crude extracts inhibited human mesangial cell proliferation activated by interleukin-1beta and interleukin-6. The extracts and their median inhibitory concentrations were as follows (in microg/ml): Selaginella tamariscina (MLS-032), 56.0 +/- 2.0; Ixeris chinensis (MLS-033), 62.7 +/- 1.7; Polygonum hypoleucum Ohwi (MLS-034), 25.0 +/- 1.5; Scutellaris rivularis (MLS-036), 39.6 +/- 1.1; Condonacanthus paucifiorus (MLS-042),63.6 +/- 2.6; Xanthium strumarium (MLS-043), 42.8 +/- 1.3; Daemonoropus margaritae (MLS-044), 56.1 +/- 1.9. These findings indicate that human mesangial cells were most sensitive to MLS-034 treatment. These herbs also decreased interleukin-1beta and tumor necrosis factor-alpha production. Moreover, TNF-alpha mRNA expression was inhibited by MLS-034. It is unlikely that cytotoxicity was involved, because no cell deaths were observable. We hypothesize that the inhibitory mechanisms of these Chinese herbs may be related to the impairments of gene expression and production of cytokines in human mesangial cells. Plans are underway for the isolation of pure compounds from these Chinese herbs and the elucidation of their mechanisms of action.
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PMID:Chinese herbs as modulators of human mesangial cell proliferation: preliminary studies. 966 76

Low serum albumin and low serum cholesterol levels are among the most consistent predictors of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Hypoalbuminemia is often interpreted as a marker of poor nutrition, but serum albumin and cholesterol levels can also be low as part of a cytokine-mediated acute-phase reaction to acute or chronic inflammation. Here we report the results from a 900-day prospective study designed to determine whether tumor necrosis factor-alfa (TNF-alpha) and interleukin-6 (IL-6) predict serum albumin and cholesterol levels and mortality in a group of 90 ambulatory, adult hemodialysis patients with no acute infection, hospitalization or surgery, and no known acquired immunodeficiency syndrome (AIDS), malignancy, or liver disease. Measurable levels of TNF-alpha and/or IL-6 were found in 89 of 90 patients. Significant relationships were found between TNF-alpha and IL-6 and the degree of hypoalbuminemia and dyslipoproteinemia. IL-6 was the strongest predictor of mortality in univariate and multivariate analysis, followed by age, albumin level, and body mass index (BMI). Although the cause of hypercytokinemia was not addressed in this study, the data support the view that hypoalbuminemia and hypocholesterolemia are negative acute-phase responses to inflammatory stimuli. These results suggest that efforts to identify the nature of the stimuli for cytokine production and to lower cytokine levels in hemodialysis patients might be effective in improving the survival of patients undergoing hemodialysis.
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PMID:Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients. 966 31

The mechanism of deposition of IgA in the renal mesangium in primary IgA-nephropathy is poorly understood. It has been suggested that membrane receptors for IgA on mesangial cells (MC) of the kidney may be involved. To obtain more insight in the occurrence of the myeloid receptor for IgA (CD89) on MC, both in situ and in culture, rabbit and goat polyclonal antibodies and mouse monoclonal antibody against recombinant CD89 were raised. Kidney sections from five control subjects and five patients with primary IgA-nephropathy failed to be positive for CD89 in the mesangium, using our polyclonal and monoclonal antibodies. Also, five primary human MC cultures assessed for CD89 expression showed no protein expression of CD89. Furthermore, reverse transcription-PCR failed to detect mRNA expression of CD89 in the cultured MC. It was demonstrated that all five human primary MC bound human IgA in a dose-dependent manner, which was not inhibitable by blocking monoclonal anti-CD89 antibody (My43). In contrast, binding of IgA to U937 cells was blocked efficiently by My43. Finally, incubation of human MC with either human or rat IgA led to increased interleukin-6 production, whereas only human IgA, but not rat IgA, was able to bind to human CD89. Therefore, it is concluded that human MC do not express CD89 (to a significant extent). These results strongly suggest that binding of IgA to human MC occurs via an IgA receptor distinct from CD89.
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PMID:Human mesangial cells in culture and in kidney sections fail to express Fc alpha receptor (CD89). 1020 61

Cytokines are small regulatory peptides with diverse functions. They regulate the immune system and modulate the inflammatory response, both of which are implicated in vesico-ureteric reflux (VUR) and associated reflux nephropathy (RN). The cytokine profile in VUR and RN has yet to be fully investigated. Blood was obtained from three subject groups immediately after induction of anaesthesia: group A [subjects with VUR and established RN, (N=9)]; group B [VUR alone but no associated RN, (N=6)]; and group C [age- and sex-matched controls with no history of urinary sepsis, (N=14)]. Serum cytokine levels of tumour-necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), soluble TNF receptor-1 (sTNF-R1), and interleukin-8 (IL-8) were measured using standard ELISA technique. Serum levels of IL-6 were higher in group A subjects (1.798-4.638 pg/ml, median 3.253 pg/ml) than controls (1.531-2.078 pg/ml, median 1.798 pg/ml). There was no significant difference in levels in group B subjects (1.498-3. 048 pg/ml, median 1.948 pg/ml) and controls. These same relationships were observed for levels of TNF-alpha (group A: 8. 501-14.471 pg/ml, median 13.483 pg/ml; group B: 7.088-10.650 pg/ml, median 8.886 pg/ml; group C: 6.746-13.344 pg/ml, median 7.671 pg/ml) and sTNF-R1 (group A: 690.34-5780.74 pg/ml, median 1197.38 pg/ml; group B: 366.65-1401.62 pg/ml, median 592.82 pg/ml; C: 313.49-636.33 pg/ml, median 504.17 pg/ml). IL-8 was not significantly elevated in any of the study groups (A or B) compared with control group C (group A: 27.08-56.38 pg/ml, median 31.35 pg/ml; group B: 29.90-35. 87 pg/ml, median 31.35 pg/ml; group C: 25.05-30.22 pg/ml, median 29. 90 pg/ml). These results suggest there may be an immunological basis to RN.
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PMID:Serum cytokine profile in reflux nephropathy. 1066 39

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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