title: Increased excretion of tumor necrosis factor alpha and interleukin 1 beta in urine from patients with IgA nephropathy and Schönlein-Henoch purpura.
abstract: Urinary proteins (5 mg/ml) collected from a group of 16 patients including 13 with IgA nephropathy and 3 with Schönlein-Henoch purpura (SHP) and from a control group consisting of 6 patients with diabetic nephropathy, 5 patients with hypertensive nephrosclerosis, and 5 healthy hospital staff members were studied for the contents of interleukins (IL) 1 beta, 2, 4, 6, and 12 and tumor necrosis factor alpha (TNF-alpha). Eleven patient with IgA nephropathy or SHP (11/16) but only 1 of the controls (1/16) had TNF-alpha activity in urinary proteins (p < 0.01). The IL-1 beta activity exhibited a similar tendency but to a lesser extent (10 of 16 patients with IgA nephropathy or SHP vs. 2 of 16 with other conditions, p < 0.05). Conversely, the detection rates of IL-2, IL-4, and IL-6 in both groups were not significantly different. IL-12 was not found in any of the samples from both groups. Sera and nonpurified urine samples from the same individuals were also measured for cytokines. IL-1 beta, IL-2, IL-4, and IL-12 were absent in all these samples, but TNF-alpha was found in four of the serum samples from patients with IgA nephropathy. Urinary proteins (2 mg/ml) were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whereby peptides of 52, 49, 45, 34, 30, and 11 kD could be demonstrated in the patients with IgA nephropathy or SHP. Urinary proteins (200 micrograms/ml from patients with IgA nephropathy or SHP exerted a mitogen-like effect on the normal human mononuclear cells, as demonstrated by 3H-thymidine incorporation. In addition, these urinary proteins (400 micrograms/ml) enhanced the proliferative activity of the cultured rat glomerular mesangial cells. The exaggerated proliferation of rat glomerular mesangial cells exerted by urine proteins from 2 patients with active disease was markedly suppressed after treatment with glucocorticoids/cyclophosphamide. These results suggest that patients with IgA nephropathy or SHP can excrete excessive amounts of TNF-alpha and IL-1 beta in the urine. The inconsistent presence of these two cytokines in urine and serum may indicate that they can be produced locally and that they are implicated in the development of mesangial inflammation and glomerular damage.
authors.affiliation: Section of Nephrology, Veterans General Hospital-Taipei, Taiwan/ROC.
authors.forename: T H
authors.initials: TH
authors.lastname: Wu
authors.forename: S C
authors.initials: SC
authors.lastname: Wu
authors.forename: T P
authors.initials: TP
authors.lastname: Huang
authors.forename: C L
authors.initials: CL
authors.lastname: Yu
authors.forename: C Y
authors.initials: CY
authors.lastname: Tsai
mesh_terms: D000293:Adolescent; D000328:Adult; D000645:Ammonium Sulfate; D019138:Antibodies, Blocking; D015415:Biomarkers; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000652:urine; D004586:Electrophoresis; D005260:Female; D005920:Glomerular Mesangium / Q000503:physiopathology; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000503:physiopathology / Q000652:urine*; D006801:Humans; D011695:IgA Vasculitis / Q000150:complications / Q000503:physiopathology / Q000652:urine*; D007375:Interleukin-1 / Q000276:immunology / Q000652:urine*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011507:Proteinuria; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000652:urine*
chemical_list: D019138:Antibodies, Blocking; D015415:Biomarkers; D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D000645:Ammonium Sulfate