title: Mononuclear cells in glomeruli and cytokines in urine reflect the severity of experimental proliferative immune complex glomerulonephritis.
abstract: Immunohistochemical methods were used to investigate the role of macrophages in the progression of proliferative immune complex glomerulonephritis. The mononuclear cell component of glomerular inflammation was analysed in three different stages of chronic serum sickness, each of which was clearly distinguished by criteria of kidney function. Urinary excretion of the macrophage secretory products interleukin-1 and tumour necrosis factor was also evaluated in relation to the functional severity of kidney disease. T lymphocytes and macrophages began to accumulate in glomeruli at the onset of proteinuria, but not before. Urinary excretion of interleukin-1 also began with proteinuria. Proteinuria increased in direct correlation with increases in the number of glomerular macrophages. Development of the most severe stage of glomerulonephritis, characterized by cachexia, declining kidney function, and necrotizing glomerular pathology, was accompanied by the disappearance of T cells from glomeruli and the expression of highly abnormal phenotypes by most macrophages. In addition, there was a switch from urinary excretion of interleukin-1 to excretion of tumour necrosis factor. The progression of proliferative immune complex glomerulonephritis was associated with qualitative as well as quantitative changes in glomerular macrophage populations. Differentiation and/or activation of those glomerular macrophages may have resulted from local T cell-mediated immunoregulation. Measurements of urinary cytokine excretion provided a reliable means of monitoring disease progression. The local action of tumour necrosis factor probably contributed to declining kidney function in the most severe stage of disease.
authors: Department of Microbiology, School of Medicine, State University of New York, Buffalo 14214.
authors: B
authors: B
authors: Noble
authors: K
authors: K
authors: Ren
authors: J
authors: J
authors: Taverne
authors: J
authors: J
authors: Dipirro
authors: J
authors: J
authors: Van Liew
authors: C
authors: C
authors: Dijkstra
authors: G
authors: G
authors: Janossy
authors: L W
authors: LW
authors: Poulter
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000652:urine*; D016207:Cytokines; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology* / Q000652:urine; D007105:Immune Complex Diseases / Q000276:immunology* / Q000652:urine; D007375:Interleukin-1 / Q000652:urine; D007678:Kidney Glomerulus / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000652:urine
chemical_list: D001685:Biological Factors; D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha