Abstract: SA-PO0311
Renoprotective Role of Interleukin 6 in Diabetic Kidney Disease
Session Information
- Diabetic Kidney Disease: Basic and Translational Science Advances - 2
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Mutig, Kerim, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
- Gubernatorova, Ekaterina O., Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation
- Litvinova, Anna, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation
- Gorshkova, Ekaterina, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation
- Purtova, Svetlana, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation
- Drutskaya, Marina S., Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation
Background
Sterile inflammation in diabetic kidney disease (DKD) involves complex cytokine interplay, with Interleukin 6 (IL-6) playing a dual role: proinflammatory via its soluble receptor and cytoprotective through the membrane-bound receptor. The present study characterizes cytoprotective vs. proinflammatory IL-6 effects in a mouse DKD model.
Methods
DKD was induced in IL-6 knockout (IL-6-/-) vs. wild-type (WT) mice using streptozotocin (STZ). The progress of DKD was evaluated during four weeks after STZ injections by monitoring blood and urinary parameters, evaluation of molecular markers of cellular stress, and final assessment of kidney morphology.
Results
Both genotypes responded to STZ with similar increases in blood glucose and water intake confirming successful development of diabetes. At the end of experiments STZ-treated IL-6-/- mice developed significant proteinuria, hypoalbuminemia, and hypoproteinemia, whereas only a moderate hypoalbuminemia was present in WT controls. Diabetic IL-6-/- but not WT mice exhibited increased serum alanine aminotransferase levels suggesting stronger kidney or liver damage. Histological analysis using PAS, Sirius Red, and Masson’s trichrome methods pointed to greater DKD-associated profibrotic changes in kidneys from IL-6-/- compared to WT mice. Furthermore, diabetic IL-6-/- mice displayed amplified expression of genes involved in endoplasmic reticulum stress and apoptosis (ATF4, ATF6b, XBP1, Havcr1), underscoring molecular pathways driving renal injury in the absence of IL-6-mediated cytoprotection.
Conclusion
Renoprotective effects of IL-6 in a mouse DKD model were evident at functional, tissue and cellular levels, suggesting that therapeutic IL-6 inhibition – though beneficial in other conditions – may exacerbate DKD pathology. This study highlights the critical need for context-specific evaluation of IL-6 inhibiting agents in diabetic patients.