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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical episodes of IgA nephropathy coincide recurrently with microbial infections. Cytokines produced during such infections may play a role in the pathogenesis of IgA-associated glomerulonephritis. To test this hypothesis, we examined the influence of passively administered proinflammatory cytokines (IL-1, IFN-gamma and IL-6) on the development of glomerulonephritis in an experimental model of IgA nephropathy. Glomerular IgA immune deposits were induced in mice by administration of IgA anti-phosphorylcholine (PC) with either a PC-containing carbohydrate antigen of Pneumococcal C polysaccharide (PnC) or a protein antigen of PC-conjugated bovine serum albumin (PC-BSA). The effect of IL-1 on the IgA-PC-BSA induced glomerular changes resulted in an increase of mesangial hypercellularity that was associated with mild proteinuria and hematuria. Mice treated with IL-1 and IgA-PnC developed diffuse proliferative glomerulonephritis with proteinuria and hematuria. In contrast, IL-6 treatment with IgA-PC-BSA of IgA-PnC failed to exert any significant renal effect. The combination of IL-6 and IL-1, however, intensified the mesangial hypercellularity of the IgA-PC-BSA, and induced severe proliferative glomerulonephritis with inflammatory monocytes and neutrophils infiltrates in the IgA-PnC treated mice. These glomerular changes were also accompanied by increased proteinuria and hematuria. Similarly, the combination of IFN with IL-1 produced histologic changes and compromised renal function more than IFN or IL-1 exerted independently. These results suggest that extrarenal cytokines influence the renal response to IgA immune deposits. We also conclude that a synergy of multiple cytokines and nephritogenic antigens immobilized in glomerular IgA immune deposits may lead to rapid progression of IgA-associated glomerulonephritis.
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PMID:Extrarenal cytokines modulate the glomerular response to IgA immune complexes. 140 17

Rats receiving a single dose of adriamycin (7.5 mg/kg) develop heavy proteinuria and histologic lesions similar to those found in minimal change nephrotic syndrome in humans. We found that whole isolated glomeruli from rats injected with adriamycin secreted an IL-1-like cytokine which closely resembled macrophage IL-1. Maximal IL-1-like activity was detected on day 14 of the experiment when rats were heavily proteinuric. Administration of anti-IL-1 antiserum to rats with adriamycin-induced nephrosis provoked a transient but marked reduction in the urinary protein excretion. Our results indicate that IL-1-could be an important mediator implicated in the development of proteinuria in this experimental nephropathy.
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PMID:Effect of anti-interleukin-1 administration to rats with adriamycin-induced nephrosis. 158 78

Rats receiving a single dose of adriamycin (7.5 mg/kg) develop heavy proteinuria and morphological abnormalities similar to those observed in minimal change nephrotic syndrome in humans. A concomitance between enhanced I-a display by resident glomerular macrophages, IL-1-like cytokine secreted by whole isolated rat glomeruli and proteinuria was observed in adriamycin-injected rats during the experimental protocol. In addition, in vitro studies have shown that after stimulation with adriamycin or lipopolysaccharide (LPS) this cytokine is mainly produced by resident glomerular macrophages in culture. Although the precise mechanism of proteinuria in this model needs to be further studied, our results indicate that IL-1-like cytokine could be an important mediator implicated in the structural and functional disturbances occurring at the glomerular capillary wall level in adriamycin nephrosis.
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PMID:IL-1-like production in adriamycin-induced nephrotic syndrome in the rat. 173 26

Degradation of matrix in normal glomeruli occurs through the action of neutral metalloproteinases which are in turn regulated by specific inhibitors. Both of these proteins are secreted by mesangial cells. Macrophages and IL-1 enhance the secretion of the proteinase. Decreased production of the metalloproteinase and for increased secretion of its inhibitor may lead to matrix accumulation. Neutrophil serine paternases degrade glomerular basement membrane (GBM) in vitro. In both animal and human disease urine excretion of these enzymes is accompanied by proteinuria and the presence of GBM-fragments. Further knowledge of the processes involved in matrix degradation may lead to improved therapy of glomerular disease.
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PMID:Proteinases and the glomerulus: their role in glomerular diseases. 228 May 77

From January 1986 to December 1988, 8 patients with lupus nephritis did not respond to the administration of two courses of methylprednisolone pulse therapy and cyclophosphamide treatment for 56 days. These cases then received intravenous prostaglandin E1 (PGE1) for 3 weeks. All of them had a good response with decreased proteinuria and azotemia; serum C3 and C4 levels and creatinine clearance also increased. Both OKT4+ and OKT8+ cells increased, and the OKT4/OKT8 ratio was almost normal. The macrophage functions included increased production of interleukin 1 and gamma-interferon. The capacity to synthesize immunoglobulin after pokeweed mitogen stimulation was reduced, the circulating immune complexes lowered, and glomerular IgG deposits decreased in the two class IV follow-up biopsy cases after PGE1 therapy. These clinical improvements after PGE1 therapy are probably related to the modulation of macrophage T-B cell interaction, enhancement of reticuloendothelial system function, and increased glomerular capillary flow.
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PMID:Improvement in steroid and immunosuppressive drug resistant lupus nephritis by intravenous prostaglandin E1 therapy. 237 Sep 25

This study examined the frequency of anti-vascular endothelial cell (VEC) antibodies (Ab) in 72 patients with IgA nephropathy (IgAN), and their possible relationship to clinical and histological parameters of the disease. An enzyme immunoassay was developed to measure the binding of sera to endothelial cells grown to a confluent monolayer. Thirty-two percent of IgAN patients had serum anti-VEC activity as compared to 4% of controls (P = 0.004) and 9% of patients with other primary glomerulonephritis (P = 0.017). This was shown to be due to anti-HLA class I Abs in 6 of the 23 IgAN patients, and in the 1 control positive for anti-VEC activity. Hence 17 IgAN patients had anti-VEC Abs, predominantly of the IgA subclass. Stimulation of the endothelial cells with interferon-gamma and interleukin 1 did not increase the binding of these Abs. There was no correlation with circulating immune complex (IC) levels, and removal of ICs in positive sera by ultracentrifugation did not decrease anti-VEC binding. Significant correlations were found between anti-VEC Abs and proteinuria greater than 1 g/day (P = 0.044), as well as IgA anti-VEC Abs and C3 or IgA deposition in renal arterioles (P = 0.048). These IgA Abs may be an important marker of pathogenetic activity in IgAN.
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PMID:Anti-vascular endothelial cell antibodies in patients with IgA nephropathy: frequency and clinical significance. 314 14

Requirements for leukocyte adhesion molecules as well as cytokines have been determined in the rat model of acute nephrotoxic nephritis. Proteinuria (at 24 h) and neutrophil accumulation in renal glomeruli (at 6 h) have been used as the endpoints. For full accumulation in glomeruli of neutrophils as well as full development of proteinuria, requirements have been demonstrated for TNF alpha, (but not IL-1), CD11b (but not CD11a), very late arising-4 (CD49d/CD29), and intercellular adhesion molecule-1 but not endothelial leukocyte adhesion molecule-1 (E-selectin). By immunohistochemical approaches, infusion of antibody to glomerular basement membrane induced glomerular upregulation of intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, and vascular adhesion molecule-1. Treatment of rats with anti-TNF alpha or soluble recombinant human TNF receptor-1 blocked this expression. Renal arterial infusion of TNF alpha induced glomerular expression of all three endothelial adhesion molecules, but infusion of IL-1 beta did not. These data suggest that, in neutrophil and complement-dependent anti-glomerular basement membrane-induced acute nephritis in rats, there are selective requirements for cytokines, beta 1 and beta 2 integrins, and endothelial adhesion molecules. These requirements contrast with those found in other vascular beds in which complement and neutrophil-induced vascular injury has been induced by deposition of immune complexes.
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PMID:Requirements for leukocyte adhesion molecules in nephrotoxic nephritis. 767 12

The contribution of IL-1 to leukocyte infiltration in anti-glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was examined by the administration of a specific IL-1 receptor antagonist (IL-1ra). Lewis rats received anti-GBM Ab or normal rabbit serum and were treated with either 0.9% saline or 6 mg IL-1ra over a 24-h time period. Plasma IL-1ra concentration was 2,659 +/- 51 ng/ml 4 h after anti-GBM Ab and IL-1ra administration. PMN and monocyte/macrophage infiltration declined 39% (9.8 +/- 1.9 to 6.0 +/- 1.5 PMN/glomerulus, P < 0.001) and 29% (4.9 +/- 0.8 to 3.5 +/- 0.8 ED-1 cells/glomerulus, P = 0.002) with IL-1ra treatment at 4 h, respectively. Similarly, the number of glomerular cells staining for lymphocyte function-associated molecule-1 beta (CD18) declined 39% from 16.7 +/- 1.9 to 10.7 +/- 1.6 cells/glomerulus at 4 h (P = 0.0001). This was associated with a decrease in glomerular intracellular adhesion molecule-1 expression. The mean glomerular intracellular adhesion molecule-1 score in anti-GBM Ab GN rats treated with IL-1ra was less than that of rats administered anti-GBM Ab and 0.9% saline at 4 (2.0 +/- 0.2 vs 2.5 +/- 0.2, P < 0.05) and 24 (2.5 +/- 0.1 vs 3.1 +/- 0.2, P = 0.0001) h. These immunopathologic changes correlated with a 50% reduction in proteinuria from 147 +/- 34 to 75 +/- 25 mg/d (P < 0.002). Treatment with IL-1ra did not affect the steady state mRNA expression of either IL-1 beta or TNF alpha. An increase in the IL-1ra dose to 30 mg given within the initial 4 h provided no additional benefit. The decline in PMN and monocyte/macrophage infiltration of the glomerulus at 4 h was similar to that found in the initial study. Furthermore, the protective benefit of IL-1ra was abrogated by doubling the dose of the anti-GBM Ab GN, despite administering high dose IL-1ra (30 mg). In these studies, detectable IL-1ra was found in the serum of untreated anti-GBM Ab GN controls. These data suggest a positive yet limited role for IL-1ra in the therapeutic intervention of anti-GBM Ab GN.
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PMID:Interleukin-1 receptor antagonist ameliorates experimental anti-glomerular basement membrane antibody-associated glomerulonephritis. 790 69

Due to the immunopharmacological profile of the recombinant IL-1 receptor (IL-1-R) and its potential to modulate biological activity in various inflammatory autoimmune disease models, we further elucidated its disease modifying activity on the development of a systemic lupus erythematosus (SLE)-like disease in BDF1 hybrid mice and in MRL/lpr autoimmune mice. Treatment of BDF1 mice with the IL-1-R during the induction phase resulted in a strong inhibition of the development of a glomerulonephritis, prolonged the survival time and improved the survival rate. Even a therapeutic effect was demonstrated when this receptor was given after the appearance of clinical symptoms. Treating MRL/lpr mice, which develop spontaneously a SLE-like disease, with the IL-1-R resulted in an inhibition of the developing glomerulonephritis and splenomegaly, in a reduction of swollen lymph nodes and in a decrease of autoantibody formation. Even in the established autoimmune disease of MRL/1 pr mice the IL-1-R reduced proteinuria, the levels of autoantibodies and also improved the survival rate.
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PMID:Immunoregulation of SLE-like disease by the IL-1 receptor: disease modifying activity on BDF1 hybrid mice and MRL autoimmune mice. 827 48

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


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