Interleukin-11 attenuates nephrotoxic nephritis in Wistar Kyoto rats

Interleukin-11 (IL-11) is a multifunctional cytokine with anti-inflammatory activity. The effect of IL-11 was studied in an experimental model of necr otizing glomerulonephritis induced in Wistar Kyoto rats by an injection of anti-glomerular basement membrane antibody (nephrotoxic serum). Intraperito neal injection was chosen as the route of IL-11 administration in all exper iments. In experiment 1, recombinant human IL-11 (1360 mug) was given 2 h b efore nephrotoxic serum, then once daily until day 6. In experiment 2, a lo wer dose of IL-11 (800 mug/d) was used. Rats were treated either with IL-11 400 mug twice daily intraperitoneally or with 800 Ag once daily intraperit oneally for 6 d. In experiment 3, the lower dose of IL-11 was given 2 h bef ore nephrotoxic serum, then twice daily until day 2. In experiment 1, IL-11 significantly reduced proteinuria (13.2 +/- 3.3 versus 63.2 +/- 4.3 mg/24 h). fibrinoid necrosis (0.58 +/- 0.08 versus 1.52 +/- 0.06 quadrants/glomer ular cross section [gcs]), macrophage infiltration (ED1-positive cells, 24. 4 +/- 1.8 versus 39.3 +/- .9 cells/gcs), apoptosis (1.11 +/- 0.1 versus 2.3 9 +/- 0.2 apoptotic bodies/gcs). and proliferating cell nuclear antigen-pos itive cells (24.4 +/- 2.0 versus 37.3 +/- 2.3 cells/gcs). Inducible nitric oxide synthase-positive cells were significantly increased (3.1 +/- 0.3 ver sus 2.0 0.2 cells/gcs). In experiment 2, a lower dose of IL-11 significantl y reduced proteinuria and fibrinoid necrosis. Macrophage infiltration was s imilar in treated and control groups, although the number of sialoadhesin-p ositive macrophages (ED3+) was significantly reduced in the IL-11-treated r ats. In experiment 3, quantitative competitive reverse transcriptase-polyme rase chain reaction showed that the mRNA ratio of IL-1 beta/beta -actin in the treated rats was reduced compared with controls. By the use of probes d esigned from mouse IL- I I receptor alpha -chain sequence, it was also show n that rat mesangial cells and macrophages expressed IL-11 receptor alpha - chain, demonstrating that they were capable of responding to IL-11. In this model of necrotizing glomerulonephritis, high-dose IL-11 treatment markedl y reduced both proteinuria and fibrinoid necrosis. At the lower dose, there was a reduction in glomerular injury and macrophage sialoadhesin expressio n. but without an alteration of macrophage numbers, suggesting that IL-11 m ay be acting in part to reduce macrophage activation.