interleukin-8 and Proteinuria

End-stage renal disease (ESRD) due to type 2 diabetic nephropathy is a very common condition which is increasing in prevalence, and is associated with high global levels of mortality and morbidity. Both proteinuria and transforming growth factor-β (TGF-β) may contribute to the development of ESRD in patients with diabetic nephropathy. Experimental studies indicate that turmeric improves diabetic nephropathy by suppressing TGF-β. Therefore, this study investigated the effects of turmeric on serum and urinary TGF-β, interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α), as well as proteinuria, in patients with overt type 2 diabetic nephropathy.. A randomized, double-blind and placebo-controlled study was carried out in the Diabetes Clinic of the Outpatient Department of Shiraz University of Medical Sciences on 40 patients with overt type 2 diabetic nephropathy, randomized into a trial group (n = 20) and a control group (n = 20). Each patient in the trial group received one capsule with each meal containing 500 mg turmeric, of which 22.1 mg was the active ingredient curcumin (three capsules daily) for 2 months. The control group received three capsules identical in colour and size containing starch for the same 2 months.. Serum levels of TGF-β and IL-8 and urinary protein excretion and IL-8 decreased significantly comparing the pre- and post-turmeric supplementation values. No adverse effects related to turmeric supplementation were observed during the trial.. Short-term turmeric supplementation can attenuate proteinuria, TGF-β and IL-8 in patients with overt type 2 diabetic nephropathy and can be administered as a safe adjuvant therapy for these patients.

Topics: Administration, Oral; Curcuma; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dietary Supplements; Double-Blind Method; Female; Humans; Interleukin-8; Male; Middle Aged; Phytotherapy; Proteinuria; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Topics: Animals; Cell Line; Female; Humans; Hydrolyzable Tannins; Intercellular Adhesion Molecule-1; Interleukin-8; Kidney; Lupus Erythematosus, Systemic; Lupus Nephritis; Mice; Mice, Inbred NZB; NIH 3T3 Cells; Podocytes; Proteinuria; Receptor, PAR-2; Signal Transduction; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

To investigate the association between single nucleotide polymorphisms (SNPs) in endothelial nitric oxide synthase (eNOS) and interleukin-8 (IL-8) genes and risk of developing bevacizumab-related adverse events in metastatic breast cancer (mBC) patients.. mBC patients candidate to receive bevacizumab-based chemotherapy were enrolled in this pharmacogenetic study. eNOS c.-813C>T and c.894G>T, and IL-8 c.-251A>T were analyzed by real time PCR on genomic DNA extracted from peripheral blood. Univariate analysis was performed to test the association between each SNP and treatment-related toxicities.. Seventy-six mBC patients were enrolled in the present study. Patients carrying the homozygous variant eNOS c.-813TT genotype showed a statistically significant occurrence of any grade proteinuria when compared to CT or CC genotypes (p = 0.004). No significant association of proteinuria with IL-8 SNP or hypertension with selected eNOS and IL-8 SNPs was found.. These findings suggest an association between the eNOS c.-813C>T polymorphism and the development of proteinuria in mBC patients receiving a bevacizumab-based chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Breast Neoplasms; Case-Control Studies; Female; Genetic Predisposition to Disease; Humans; Hypertension; Interleukin-8; Kaplan-Meier Estimate; Male; Middle Aged; Nitric Oxide Synthase Type III; Polymorphism, Single Nucleotide; Progression-Free Survival; Proteinuria

Diabetic glomerulosclerosis is the hardening of the renal glomeruli that can lead to kidney failure. In the early stage of glomerulosclerosis occur renal mesangial expansion and renal filtration dysfunction. Purple corn has been classified as a functional food and is rich in anthocyanins exerting potential disease-preventive activities. The in vitro study using human renal mesangial cells examined that anthocyanin-rich purple corn butanol fraction (PCB) can attenuate high glucose (HG)-promoted mesangial cell proliferation and matrix accumulation.. Cells were cultured for 3 days in media containing 33 mM glucose in the presence of 1-20 μg/mL PCB. In the in vivo animal study, db/db mice were treated with 10 mg/kg anthocyanin-rich polyphenolic extracts of purple corn (PCE) for 8 weeks.. HG enhanced mesangial production of the fibrosis biomarkers of collagen IV and connective tissue growth factor (CTGF), which was markedly attenuated by adding PCB. Such mesangial fibrosis entailed interleukin-8 activation via eliciting Tyk2-STAT signaling pathway. PCB dampened HG-promoted mesangial hyperplasia that appeared to be attributed to increased expression of platelet-derived growth factor. The 8-week administration of PCE lowered plasma glucose level of db/db mice and ameliorated severe albuminuria. Moreover, PCE lessened collagen fiber accumulation in kidney glomeruli and CTGF expression via retarding TGF-β signaling. Protein expressions of nephrin and podocin, key proteins for filtration barrier function of the glomerular capillary wall, were repressed by treating mice with PCE.. Purple corn may be a potent therapeutic agent for the treatment for diabetes-associated glomerulosclerosis accompanying proteinuria and kidney filtration dysfunction.

Topics: Albuminuria; Animals; Anthocyanins; Biomarkers; Blood Glucose; Cell Proliferation; Collagen Type IV; Connective Tissue Growth Factor; Diabetic Nephropathies; Fibrosis; Humans; Interleukin-8; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins; Mesangial Cells; Mice; Plant Extracts; Platelet-Derived Growth Factor; Proteinuria; Signal Transduction; STAT Transcription Factors; Transforming Growth Factor beta; TYK2 Kinase; Zea mays

The pathogenesis of idiopathic nephrotic syndrome (INS) remains unknown. Several findings suggest a role for the immune system. This study aimed to evaluate immune mediators in INS by measuring plasma and urinary levels of transforming growth factor beta1 (TGF-beta1), monocyte chemoattractant protein-1 (MCP-1/CCL2), regulated on activation normal T-cell expressed and secreted (RANTES/CCL5) and IL-8 (IL-8/CXCL8) in pediatric patients with INS and in age-matched healthy controls. Patients were divided according to their response to corticosteroids: steroid-sensitive (SS, n = 8), or steroid-resistant (SR, n = 24). Immune mediators were also compared in regard with disease activity (relapse and remission). Immune mediators were measured by ELISA. Plasma TGF-beta1 levels in SR patients were approximately 2.8-fold higher than control values (p < 0.05). Urinary IL-8/CXCL8 was 2.9-fold higher in INS patients in relapse (proteinuria >100 mg/m2/24 h) when compared with patients in remission (p < 0.05), and levels had a positive correlation with individual proteinuria values (p < 0.05). Urinary IL-8/CXCL8 was significantly higher in relapsed SR than in SS patients in remission. No changes in MCP-1/CCL2 and RANTES/CCL5 levels were detected. Our findings suggest that IL-8/CXCL8 and TGF-beta1 are involved in the pathogenesis of INS: IL-8/CXCL8 associated with local changes in glomerular permeability and TGF-beta1 could be related to worse response to corticosteroids.

Topics: Adolescent; Chemokine CCL2; Chemokine CCL5; Child; Female; Humans; Immunologic Factors; Interleukin-8; Male; Nephrotic Syndrome; Proteinuria; Transforming Growth Factor beta1

Using quantitative sandwich ELISA, we studied 27 patients with IgA nephropathy to determine whether the levels of urinary IL-8 might reflect the disease activity. The levels of urinary IL-8 in patients with advanced stage IgA nephropathy were significantly higher than those in the patients with the mild stage of this disease, or in the healthy controls. The results showed a positive significant correlation between the levels of IL-8 and disease activity, i.e., between levels of urinary protein and urinary casts. A significant correlation between levels of urinary IL-8 and tubular function damage was also found. It was thus suggested that measurement of urinary IL-8 might be useful in evaluating the degree of renal injuries and/or prognosis in patients with IgA nephropathy.

Topics: Adult; Creatinine; Enzyme-Linked Immunosorbent Assay; Female; Glomerulonephritis, IGA; Humans; Interleukin-8; Leukocyte Count; Male; Middle Aged; Proteinuria; Reference Values; Urine

Chemokines such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 have been implicated in recruiting leukocytes to the glomerulus during immune renal injury. To detect the expression of MCP-1 in human glomerular disease, we measured urinary MCP-1 levels in patients with a variety of glomerulopathies. These data demonstrated that MCP-1 was present in the urine of patients with glomerular disease and that patients with inflammatory glomerulopathies had higher levels of urinary MCP-1. Urinary MCP-1 correlated with the extent of proteinuria (r = 0.71, P < 0.0001), but not with serum MCP-1 levels (r = 0.14, P > 0.3). The MCP-1 present in urine was biologically active, increasing monocyte migration in a microchemotaxis assay. This activity was attenuated by the addition of anti-MCP-1 antibody to the samples. Enumerating glomerular macrophages demonstrated that glomerular inflammation was correlated with urinary MCP-1 levels (r = 0.53, P < 0.02). Individuals with light microscopic evidence of severe glomerular injury (ie, crescents, necrosis, endocapillary proliferation) had significantly higher levels of MCP-1 in their urine than patients with less severe glomerular changes (1,962 +/- 612 pg MCP-1/mg creatinine v 314 +/- 45 pg MCP-1/mg creatinine; P < 0.002). Taken together, these results suggest that urinary MCP-1 reflects the extent to which MCP-1 that is produced in the glomerulus participates in the glomerular inflammatory response.

Topics: Chemokine CCL2; Chemotaxis, Leukocyte; Creatinine; Female; Glomerulonephritis; Humans; Interleukin-8; Kidney Glomerulus; Macrophage Activation; Macrophages; Male; Necrosis; Proteinuria

In this study, viruria following Japanese encephalitis virus (JEV) infection in mice has been shown to appear earlier in pregnant than in normal mice with proteinuria and haematuria. This was related to the production of splenic macrophage derived neutrophil chemotactic factor (MDF) following JEV infection. Intravenous inoculation of MDF in mice resulted in leakage of cells, proteins and erythrocytes in the urine as a result of altered capillary permeability. The isolation of virus from kidney did not correlate with the shedding of virus in the urine. The histological examination of sections of kidneys showed no morphological damage; however, ultrastructural degenerative changes in the mesangial cells were observed following JEV infection. These data suggest that JEV-induced macrophage derived factor regulates the leakage of proteins, erythrocytes and cells into the urine.

Topics: Acute Disease; Animals; Antibodies, Viral; Chemotaxis, Leukocyte; Encephalitis Virus, Japanese; Encephalitis, Japanese; Female; Fluorescent Antibody Technique; Hematuria; Interleukin-8; Kidney; Mice; Pregnancy; Pregnancy Complications, Infectious; Proteinuria; Spleen

Glomerular infiltration by neutrophils is a hallmark of acute glomerulonephritis. The pathophysiological role of interleukin 8 (IL-8), a potent neutrophil chemotactic cytokine (chemokine), was explored in an animal model of acute immune complex-mediated glomerulonephritis by administering a neutralizing antibody against IL-8. Repeated injection of bovine serum albumin (BSA) into rabbits caused the deposition of immune complexes consisting of BSA and rabbit IgG in glomeruli. Histological analyses revealed a small but significant number of neutrophils in glomeruli and the fusion of epithelial cell foot processes. Concomitantly, urinary levels of protein and albumin increased markedly (3.20 +/- 0.97 and 1.39 +/- 0.53 mg/h, respectively) compared with those of untreated animals (0.77 +/- 0.21 and 0.01 +/- 0.01 mg/h, respectively). Anti-IL-8 antibody treatment decreased the number of neutrophils in glomeruli by 40% and dramatically prevented the fusion of epithelial cell foot process. Furthermore, treatment with anti-IL-8 antibody completely normalized the urinary levels of protein and albumin (0.89 +/- 0.15 and 0.02 +/- 0.01 mg/h, respectively). These results indicated that IL-8 participated in the impairment of renal functions in experimental acute immune complex-mediated glomerulonephritis through activating as well as recruiting neutrophils.

Topics: Acute Disease; Albuminuria; Animals; Antibodies, Monoclonal; Antigen-Antibody Complex; Glomerulonephritis; Interleukin-8; Kidney Glomerulus; Male; Mice; Proteinuria; Rabbits