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[The role of mononuclear leukocytes in the pathogenesis of glomerulonephritis]
Abstract:
To specify the role of mononuclear (MN) leukocytes in the development of mesangial cell proliferation, which is one of the main manifestations of glomerulonephritis, cell cultures of renal glomeruli of rats with nephrotoxic serum (NTS) nephritis were examined for the intensity of mesangial cell proliferation, the MN-leukocyte count, and for IL-1 production. The amount of mesangial cells and the intensity of their proliferation in the cultures of glomerular cells from rats with NTS nephritis were much higher than in intact rat cultures. At the same time the glomerular cultures from rats with NTS nephritis demonstrated an increase in the MN leukocyte count together with enhancement of IL-1 production. The treatment with prednisolone averted accumulation of MN leukocytes by the glomerular cultures and noticeably reduced mesangial cell proliferation. The supernatant liquid of cultures of peripheral blood MN leukocytes from patients with active nephritis suppressed human fibroblast proliferation, exerting no such action on mesangial cell culture. During the treatment with prednisolone, the supernatant liquid produced a reverse effect on fibroblast and mesangial cell cultures, which was associated with the clinical improvement of the health status. It is assumed that mesangial cell proliferation seen in nephritis may be related to infiltration of the glomeruli by MN leukocytes and to elevated production by them of IL-1 and that the therapeutic action of prednisolone may be determined by suppression of these processes.
Insights
Mononuclear leukocytes and IL-1 contribute to mesangial cell proliferation in glomerulonephritis. Prednisolone treatment reduces these factors, suggesting a therapeutic mechanism.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Glomerulonephritis is characterized by mesangial cell proliferation.
- The role of mononuclear leukocytes in this process is not fully understood.
Purpose of the Study:
- To investigate the role of mononuclear (MN) leukocytes in mesangial cell proliferation in nephrotoxic serum (NTS) nephritis.
- To examine the impact of IL-1 production by MN leukocytes.
- To assess the therapeutic effect of prednisolone.
Main Methods:
- Cell cultures of rat renal glomeruli with NTS nephritis.
- Quantification of mesangial cell proliferation and MN leukocyte count.
- Measurement of IL-1 production.
- Assessment of supernatant effects on fibroblast and mesangial cell cultures.
- In vivo prednisolone treatment.
Main Results:
- NTS nephritis cultures showed increased mesangial cell proliferation, MN leukocyte count, and IL-1 production compared to controls.
- Prednisolone treatment reduced MN leukocyte accumulation and mesangial cell proliferation.
- Supernatant from active nephritis MN leukocytes suppressed fibroblast proliferation but not mesangial cells.
- Prednisolone treatment reversed this effect, correlating with clinical improvement.
Conclusions:
- Mesangial cell proliferation in nephritis may be linked to glomerular MN leukocyte infiltration and IL-1 production.
- Prednisolone's therapeutic action might stem from suppressing these MN leukocyte-driven processes.
- MN leukocytes and IL-1 are potential therapeutic targets in glomerulonephritis.