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- Title
Leukemia inhibitory factor ameliorates experimental anti-GBM Ab glomerulonephritis.
- Authors
Tang, Winson W.; Qi, Meiying; Van, Gwyneth Y.; Wariner, Grace P.; Samal, Babru
- Abstract
Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that has been identified in acute and chronic inflammatory conditions such as rheumatoid arthritis, sepsis, and renal allograft rejections. We investigated the glomerular expression of LIF at 30 minutes, and 3, 6, 9, 15 and 24 hours after administration of anti-GBM Ab (<em>N</em> = 3) by the RNase protection assay. Control rats received rabbit sera and were sacrificed at 30 minutes, and 6 and 24 hours. LIF mRNA relative to GAPDH mRNA was detected at low levels within the glomeruli of occasional control rats. However, with the induction of anti-GBM Ab GN, there was a marked increase in LIF steady-state mRNA beginning at three hours which persisted through 24 hours. LIF mRNA was also detected in cultured mesangial cells stimulated with IL-1β, identifying this cell type as a potential glomerular source for this cytokine. To investigate the <em>in vivo</em> effect of LIF, Lewis rats were continuously infused with recombinant (r) human (h) LIF (∼0.5 ng/hr) or saline vehicle i.p. with ALZA osmotic pumps beginning at t = -24 hours (<em>N</em> = 8); All rats were injected with anti-GBM Ab intravenously at t = 0 (<em>N</em> = 16). LIF infusion decreased 24-hour urinary protein excretion by 85% (17 ± 15 vs. 114 ± 37 mg/day, <em>P</em> = 0.0001) and was associated with a 60% decrease in glomerular macrophage infiltration (0.8 ± 0.2 vs. 2.0 ± 0.6 ED-1 cells/glom, <em>P</em> 0.0001). The administration of rhLIF did not affect the binding of the anti-GBM Ab to glomeruli. The beneficial effects of LIF were associated with a decrease in glomerular MCP-1 (56%), IL-1 (41%) and TNF (17%) steady state mRNA expression. The latter was associated with a 29% decrease in TNF-α protein expression within the glomerular lysate of nephritic rats administered LIF when compared with control rats. These data demonstrate a potential role for LIF in the therapy of anti-GBM Ab GN.
- Subjects
LEUKEMIA; RHEUMATOID arthritis; PUMPING machinery; AUTOIMMUNE diseases; BLOOD hyperviscosity syndrome; THERAPEUTICS
- Publication
Kidney International, 1996, Vol 50, Issue 6, p1922
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.1996.514