Abstract: TH-PO0415
Interleukin-6 Monoclonal Antibody Treatment of Experimental Autoimmune Glomerulonephritis in CD1 Mice
Session Information
- Glomerular Diseases: Autoimmune Diseases
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Reynolds, John, University of Bedfordshire, Luton, England, United Kingdom
- Pusey, Charles D., Imperial College London, London, England, United Kingdom
Background
Experimental autoimmune glomerulonephritis (EAG) can be induced in CD1 mice by immunisation with the recombinant NC1 domain of the alpha 3 chain of type IV collagen (α3(IV)NC1). In this murine model of EAG, CD1 mice develop circulating and deposited anti-glomerular basement membrane (GBM) antibodies, and focal necrotising glomerulonephritis with crescent formation, by week 12 after immunisation. Interleukin-6 (IL-6) is a cytokine that orchestrates inflammation and immunity by activating STAT3 signalling, driving acute-phase protein production and modulating multiple adaptive immune functions. It is crucial for Th17 differentiation and for determining the Th17/Treg balance, making it a key regulator of tolerance versus inflammation. Blockade of the IL-6 receptor is effective in several chronic inflammatory diseases. The aim of this study was to examine the role of anti-interleukin 6 (IL-6) monoclonal antibody (mAb) therapy in the treatment of established EAG.
Methods
Groups of CD1 mice with EAG (n=10) were given a weekly subcutaneous injection of anti-IL-6 mAb (54E07, UCB), or an irrelevant mAb (101.4, UCB) at a dose of 30mg/kg, starting at week 6 after immunisation, when disease was established.
Results
Animals given the anti-IL-6 mAb showed a significant reduction in the urinary albumin/creatinine ratio (control 6.9mg/mmol vs anti-IL-6 mAb 4.1mg/mmol, p<0.04), glomerular abnormalities (control 54% vs anti-IL6 mAb 33%, p<0.006) and glomerular T cells (control 3.9/glomerulus vs anti-IL-6 mAb 2.2/glomerulus, p<0.0003) by week 12, when compared to controls. No significant reduction was observed in the levels of circulating antibodies directed towards α3(IV)NC1, or in the intensity of deposits of IgG on the GBM, suggesting an effect on cell-mediated or innate immunity.
Conclusion
The results from this study demonstrate that anti-IL-6 mAb therapy is effective in the treatment of established EAG. This confirms the importance of IL-6 in the development of glomerular inflammation, and implies that IL-6 may represent a valid therapeutic target in the treatment of human glomerulonephritis.
Funding
- Government Support – Non-U.S.