Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied mRNA and protein expression of interleukins (IL) and tumor necrosis factor (TNF) in renal tissues biopsied from 40 patients with IgA nephritis. Immunofluorescent staining with antibodies to IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta was intense in the cytoplasm of cells in glomeruli, which were dual-stained with an anti-monocyte-macrophage antibody. In addition, moderate immunofluorescence for TNF-alpha, and weak staining for IL-1 alpha and IL-6 were occasionally found in resident glomerular cells. Immunoperoxidase-in situ hybridization dual-labeling revealed that IL-1 alpha, IL-6, and TNF-alpha mRNA signals were present in intraglomerular cells reactive with anti-monocyte-macrophage antibody, which further supported the immunofluorescent findings. Cells expressing IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta were also observed in the interstitium. Most of these cells were also labeled with the anti-monocyte-macrophage antibody. The number of IL-1 alpha, IL-6, and TNF-alpha-positive cells infiltrating the glomerulus significantly correlated with mesangial hypercellularity. IL-8 and TNF-alpha-positive intraglomerular cells were correlated with the magnitude of proteinuria. The population of interstitial cells positive for IL-1 alpha, IL-6, IL-8, and TNF-alpha was associated with the grade of tubulointerstitial changes and proteinuria. There was no correlation between local IL-1 alpha, IL-6, and TNF-alpha expression in glomeruli or interstitium and serum or urinary levels of the respective cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In situ expression of cytokines in IgA nephritis. 825 57

Interleukin 1 beta (IL-1 beta) is a potent inflammatory cytokine and IL-1 beta gene expression is elevated in the kidneys of mice with lupus nephritis. This study was designed to examine whether pharmacological administration of the IL-1 receptor antagonist (IL-1ra) would reduce the inflammation in MRL lpr/lpr mice with lupus nephritis. Human recombinant IL-1ra (RA) or saline (SA) was infused by intraperitoneal osmotic minipumps in 16 week old mice (n = 9, group RA or n = 12, group SA, respectively). Age matched MRL +/+ mice served as normal controls. At the end of 4 weeks of treatment glomerular filtration rates (5.4 +/- 0.4 vs 5.6 +/- 0.4 ml/min/kg BW), proteinuria (6.0 +/- 1.0 vs 5.5 +/- 1.2 micrograms IgG/day) glomerular volumes (571 +/- 30 vs 509 +/- 25 microns3 x 10(3)), mesangial volumes (172 +/- 23 vs 158 +/- 17 microns3 x 10(3)), and cells/glomerulus (519 +/- 51 vs 506 +/- 47) were not significantly different between RA and SA groups respectively. There was also no significant differences in spleen sizes, plasma IgG and anti-dsDNA antibody levels despite achieving levels of IL-1ra of over 0.8 microgram/ml in RA mice. Circulating IL-1 was not detected by bioassay in the plasma of diseased or normal mice. In fact, diseased, saline treated mouse plasma inhibited the cell proliferation assay in the presence of IL-1, and dilution studies showed that the endogenous inhibitors were of high titre. Although IL-1 may play a role in the renal injury of lupus nephritis, pharmacological inhibition with IL-1ra in animals with established injury is without effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Established murine lupus nephritis does not respond to exogenous interleukin-1 receptor antagonist; a role for the endogenous molecule? 853 Feb 54

The process of glomerular injury in nephrotoxic serum nephritis (NTN) is dependent on proinflammatory cytokines. In the present investigation, we assessed the actions of neutralizing antibody against IL-1 beta, TNF-alpha, IL-6 and TGF-beta 1 on glomerular injury. Marked increase in IL-1 beta and IL-6 was detected in cultured glomeruli of NTN in mice throughout the experiments from disease induction. Protein of TNF-alpha and TGF-beta 1 also increased in NTN mice 1 day after disease induction. Treatment with either IL-1 beta or TNF-alpha neutralizing antibody reduced proteinuria from 71 +/- 11.2 m g/24 hr to 32.2 +/- 6.0 (P < 0.01). 34.3 +/- 6.8 mg/24 hr (P < 0.01), respectively. Although the effect of IL-6 neutralizing antibody on proteinuria was not remarkable, the decreased creatinine clearance was improved more than that of IL-1 beta or TNF-alpha. Antibody against TGF-beta 1 had no effect on proteinuria and creatinine clearance. Treatments with IL-1 beta, TNF-alpha and IL-6 neutralizing antibodies inhibited glomerular hypercellularity in NTN mice. TGF-beta 1 neutralizing antibody suppressed the index of mesangial matrix expansion. IL-1 beta and TNF-alpha neutralizing antibodies prevented the increase in the number of macrophages in the glomeruli. The number of PCNA positive cells and alpha-smooth muscle actin expression in glomeruli was significantly reduced in the IL-6 neutralizing antibody-treated group. These results confirm the direct involvement of IL-1 beta, TNF-alpha and IL-6 in mouse NTN. We speculate that TGF-beta 1 may inhibit excessive proliferation in glomerular cells.
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PMID:[Effects of neutralizing antibodies on cytokine treatment for anti-GBM nephritis in mouse]. 901 75

This study examined the utility of interleukin-10 (IL-10), a cytokine with potent anti-macrophage and anti-Th1 activity, in the treatment of experimental anti-glomerular basement membrane (GBM) nephritis in the rat. Accelerated anti-GBM disease was induced in Sprague-Dawley rats by immunization with rabbit IgG, followed five days later by an i.v. injection of anti-GBM serum. Groups of four rats received daily s.c. injections of recombinant mouse IL-10 (500, 10 or 0.2 microgram/kg/day) or saline (control) from the time of anti-GBM serum administration until being killed on day 14. IL-10 treatment suppressed the skin DTH response as measured by skin thickness (44 to 62% decrease vs. control, p < 0.05). Compared to saline controls, IL-10 treatment had no beneficial effect on renal function, proteinuria or histological damage (including crescent formation) at any dose examined. A detailed analysis of high dose IL-10 (500 micrograms/kg/day) and saline treated animals was undertaken. Saline controls had marked glomerular macrophage accumulation and proliferation, which was augmented by IL-10 treatment (46 to 99% increases and 44 to 143% increases, respectively; p < 0.05). Immunohistochemical staining found no difference in the state of macrophage activation between the groups, as determined by the percentage of macrophages expressing IL-1 beta protein. Northern blot analysis of whole kidney RNA demonstrated an 830% increase in IL-1 beta mRNA expression in saline controls compared to normal rat kidney. High dose IL-10 treatment reduced IL-1 beta mRNA levels by 60% compared to controls (P < 0.05), but did not significantly reduce glomerular IL-1 beta protein expression. IL-10 treatment increased serum levels of rat anti-rabbit IgG, induced a rat anti-mouse IL-10 response and augmented glomerular deposition of rat C3. In conclusion, IL-10 was not an effective treatment for rat crescentic anti-GBM glomerulonephritis. This may have been due to the failure of IL-10 to achieve a sufficient reduction in IL-1 beta expression and macrophage participation in disease, or promotion of the Th2 immune response.
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PMID:Effect of interleukin-10 treatment on crescentic glomerulonephritis in rats. 918 70

We examined the functional role of interleukin (IL)-1 in mesangial cell proliferation during rat anti-Thy-1 nephritis by blocking its action with IL-1 receptor antagonist (IL-1ra). Anti-Thy-1 nephritis was induced by intravenous injection of 5 mg/kg OX-7 IgG (day 0) into inbred Wistar rats. Groups of animals (n = 9) were implanted with a micro-osmotic pump on day -1, which delivered 25 micrograms/hour human recombinant IL-1ra or saline continuously until the rats were killed at day 6, the peak of mesangial cell proliferation. Immunostaining showed that IL-1 was expressed by mesangial cells during disease. IL-1ra treatment did not affect the mild, but significant, proteinuria seen after OX-7 injection. Compared with saline treatment, IL-1ra treatment reduced mesangial cell proliferation (decreases 24% P < 0.05), glomerular hypercellularity (decreases 29%; P < 0.05), and glomerular macrophage accumulation (decreases 20%; P < 0.05). However, IL-1ra treatment had no effect on glomerular IL-1 beta mRNA expression and caused only a small reduction in the high levels of glomerular expression of platelet-derived growth factor-beta protein (decreases 6%; P < 0.05). IL-1ra caused a modest reduction in the marked up-regulation of glomerular transforming growth factor-beta 1 mRNA expression on day 6 (decreases 26%; P < 0.05), although urinary excretion of this factor was unaffected. Interestingly, IL-1ra treatment had relatively little effect upon glomerular deposition of laminin, fibronectin, and collagen type IV seen in this acute disease. In conclusion, this study has 1) demonstrated that IL-1 is expressed by mesangial cells in vivo, 2) demonstrated that IL-1 is a mesangial cell growth factor in experimental mesangioproliferative nephritis, and 3) suggests that IL-1 has little or no fibrogenic activity in mesangial matrix deposition.
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PMID:Role of interleukin-1 in mesangial cell proliferation and matrix deposition in experimental mesangioproliferative nephritis. 921 40

A case in which the enterotoxins of Staphylococcus aureus may have served as bacterial superantigens is presented. This 71-year-old man developed proteinuria and renal dysfunction after contacting pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA), coagulase type II. The infection occurred after surgery for recurrent lung cancer. Staphylococcus enterotoxins B, C, and TSST-1 were detected from the bacillus. Ten days after the onset of pneumonia, proteinuria was noted; urinary protein was as high as 1.8 g/day. The serum creatinine was elevated from 1.0 mg/dl to 3.7 mg/dl. Several immunological reactions were detected; the serum levels of IgG and IgA were increased, and the selective usage of T-cell receptor V beta (TCRV beta) was observed. Serum levels of IL-1 beta, IL-2, IL-6, IL-8, IL-12, and tumor necrosis factor alpha (TNF alpha) were also elevated. Examination of the renal biopsy specimen by light microscopy showed minor to mild mesangial proliferative glomerulonephritis. Immunofluorescence microscopy demonstrated the deposition of IgG, IgA, and C3, mainly along the capillary walls. Electron microscopy revealed electron dense deposits, mainly in the subepithelial areas, and injury to the glomerular basement membrane. When the pneumonia improved following antibiotic therapy, the renal function also improved, and proteinuria decreased. The levels of immunoglobulins and the usage of TCRV beta also decreased. Because staphylococcus enterotoxins act as superantigens, we believe this to be a typical case of superantigen-related glomerulonephritis.
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PMID:A case of superantigen-related glomerulonephritis after methicillin-resistant Staphylococcus aureus (MRSA) infection. 940 16

The objective was to study the relationship between the levels of interleukin-1 receptor antagonist (IL-1Ra) and disease activity and the acute-phase response in SLE patients with and without renal involvement. Twenty SLE patients who had distinct active clinical manifestations (eight glomerulonephritis, four systemic vasculitis without kidney involvement, nine skin rash, 12 arthritis, five serositis, four neuropsychiatric manifestations, three thrombocytopenia, one myositis and one haemolytic anaemia) were studied during a period of 8-12 months. Serum and plasma samples were taken at intervals of 6 weeks-4 months and tested for IL-1Ra, IL-1 beta, IL-6, IgG and anti-dsDNA, Clq, C3, C4 and C-reactive protein (CRP). IL-1Ra serum concentrations were increased in most SLE patients with active disease when compared to normal blood donors. However, at the time of flare, significantly higher levels of IL-1Ra were observed in patients with extra-renal disease as compared to other patients (median [range]: 363 [202-3041] and 4847 [268-27180] pg/ml for patients with and without renal involvement, respectively). This difference was not due to proteinuria. IL-1Ra levels did not correlate with SLEDAI score during flares, but they were elevated during flares in patients with extra-renal manifestations. When disease activity was at its highest, IL-1Ra concentrations correlated with IL-1 beta (r = 0.76; P < 0.001), IL-6 (r = 0.60; P < 0.01) and CRP (r = 0.61; P < 0.01), but not with C1q, C3, C4 and anti-dsDNA levels. The study showed that the pattern of inflammatory cytokines in active SLE varies in a manner that is dependent on which organs are involved. A relative absence of IL-1Ra response appears to be a feature characteristic of kidney involvement. IL-1Ra elevation clearly correlates with flares involving other organs.
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PMID:Low levels of interleukin-1 receptor antagonist coincide with kidney involvement in systemic lupus erythematosus. 944 89

Prospective study was performed on the concentrations of inflammatory cytokines IL-1, TNF and IL-6 in serum and urine (ELISA tests) were determined in the scope of total clinical-laboratory and histologic treatment in 59 patients with primary IgA nephropathy. Control group consisted of 20 healthy subjects. IL-6 was not detected either in serum of patients with IgAN, or in control examinees. TNF alpha and IL-1 beta were detected in control patients' sera and in patients with IgAN, but detected concentrations were not significantly different. IL-1 beta in urine was detected in 82.8%, TNF alpha in 90.0%, and IL-6 in 40% of our patients with IgAN. The concentrations of IL-1 beta were significantly higher compared to IL-1 beta concentrations in urine of healthy subjects and significantly correlated with the severity of glomerular and tubulointerstitial changes, as well as with the degree of proteinuria. Direct and indirect toxicity of TNF alpha on renal structures was confirmed in significantly higher concentrations of that cytokine in urine of patients with mesangial sclerosis of different percentage compared to the patients with isolated mesangial hypercellularity. Also in the patients with index of chronic lesion over 7 significantly higher TNF alpha concentrations in urine were found compared to the patients with lesion index 0-3 and 4-7. Creatinine clearance was in negative correlation with TNF alpha concentrations in urine of our patients with IgAN. Concentrations of IL-6 in urine were in correlation neither with laboratory parameters of renal function, nor with the degree of histologic changes.
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PMID:[Significance of inflammatory cytokines in the pathogenesis of IgA nephropathy]. 962 40

Interleukin-11 (IL-11) is a multifuctional cytokine with anti-inflammatory activity. The effect of IL-11 was studied in an experimental model of necrotizing glomerulonephritis induced in Wistar Kyoto rats by an injection of anti-glomerular basement membrane antibody (nephrotoxic serum). Intraperitoneal injection was chosen as the route of IL-11 administration in all experiments. In experiment 1, recombinant human IL-11 (1360 microg) was given 2 h before nephrotoxic serum, then once daily until day 6. In experiment 2, a lower dose of IL-11 (800 microg/d) was used. Rats were treated either with IL-11 400 microg twice daily intraperitoneally or with 800 microg once daily intraperitoneally for 6 d. In experiment 3, the lower dose of IL-11 was given 2 h before nephrotoxic serum, then twice daily until day 2. In experiment 1, IL-11 significantly reduced proteinuria (13.2 +/- 3.3 versus 63.2 +/- 4.3 mg/24 h), fibrinoid necrosis (0.58 +/- 0.08 versus 1.52 +/- 0.06 quadrants/glomerular cross section [gcs]), macrophage infiltration (ED1-positive cells, 24.4 +/- 1.8 versus 39.3 +/- 1.9 cells/gcs), apoptosis (1.11 +/- 0.1 versus 2.39 +/- 0.2 apoptotic bodies/gcs), and proliferating cell nuclear antigen-positive cells (24.4 +/- 2.0 versus 37.3 +/- 2.3 cells/gcs). Inducible nitric oxide synthase-positive cells were significantly increased (3.1 +/- 0.3 versus 2.0 +/- 0.2 cells/gcs). In experiment 2, a lower dose of IL-11 significantly reduced proteinuria and fibrinoid necrosis. Macrophage infiltration was similar in treated and control groups, although the number of sialoadhesin-positive macrophages (ED3+) was significantly reduced in the IL-11-treated rats. In experiment 3, quantitative competitive reverse transcriptase-polymerase chain reaction showed that the mRNA ratio of IL-1 beta/beta-actin in the treated rats was reduced compared with controls. By the use of probes designed from mouse IL-11 receptor alpha-chain sequence, it was also shown that rat mesangial cells and macrophages expressed IL-11 receptor alpha-chain, demonstrating that they were capable of responding to IL-11. In this model of necrotizing glomerulonephritis, high-dose IL-11 treatment markedly reduced both proteinuria and fibrinoid necrosis. At the lower dose, there was a reduction in glomerular injury and macrophage sialoadhesin expression, but without an alteration of macrophage numbers, suggesting that IL-11 may be acting in part to reduce macrophage activation.
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PMID:Interleukin-11 attenuates nephrotoxic nephritis in Wistar Kyoto rats. 1167 7

We investigated changes in various serum cytokines in a case of systemic lupus erythematosus (SLE) accompanied by hemophagocytic syndrome (HPS). The patient, a 15-year-old male, presented in December 1998 with bilateral salivary gland swelling and a history of fever continuing for more than 10 days. After admission, cerebellar ataxia and clouding of consciousness developed. Laboratory examinations revealed leukopenia, thrombocytopenia, high serum LDH and ferritin, hypercytokinemia, and prominent hemophagocytosis in the bone marrow. Given these findings and positive titers of antinuclear antibody, hypocomplementemia, proteinuria and pericarditis, a diagnosis of HPS with associated SLE was made. The patient was treated with high dose methylprednisolone followed by oral prednisolone and cyclosporine. The patient's clinical symptoms, abnormal blood and urine laboratory data consequently improved, and no recurrence of the symptoms has been documented. However, hemophagocytosis in bone marrow recurred with concomitantly increased serum levels of IL-6 and IL-1 beta. This case indicated that aberrant production of these inflammatory cytokines might be involved in HPS in autoimmune disease.
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PMID:[Systemic lupus erythematosus with bilateral salivary gland swelling and clouding of consciousness accompanied by hemophagocytic syndrome--a study of serial determination of serum cytokines]. 1246 29


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