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REVIEW article

Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1502299
This article is part of the Research Topic Renal Fibrosis and Renal Transplantation View all articles

Targeting Inerleukin-6 for Renoprotection

Provisionally accepted
Katerina O. Gubernatorova Katerina O. Gubernatorova 1,2*Mikhail Y. Samsonov Mikhail Y. Samsonov 3Marina Drutskaya Marina Drutskaya 1,2,4Svetlana Lebedeva Svetlana Lebedeva 5Darya Bukhanova Darya Bukhanova 3Maria Materenchuk Maria Materenchuk 5Kerim Mutig Kerim Mutig 5*
  • 1 Engelhardt Institute of Molecular Biology (RAS), Moscow, Russia
  • 2 Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Moscow Oblast, Russia
  • 3 R-Pharm JSC, Medical Department, Moscow, Russia
  • 4 Sirius University of Science and Technology, Federal Territory Sirius, Krasnodarsky Krai, Russia
  • 5 Department of Pharmacology, Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University, Moscow, Russia

The final, formatted version of the article will be published soon.

    Sterile inflammation has been increasingly recognized as a hallmark of non-infectious kidney diseases. Induction of pro-inflammatory cytokines in injured kidney tissue promotes infiltration of immune cells serving to clear cell debris and facilitate tissue repair. However, excessive or prolonged inflammatory response has been associated with immune-mediated tissue damage, nephron loss, and development of renal fibrosis. Interleukin 6 (IL-6) is a cytokine with pleiotropic effects including a major role in inflammation. IL-6 signals either via membranebound (classic signaling) or soluble receptor forms (trans-signaling) thus affecting distinct cell types and eliciting various metabolic, cytoprotective, or pro-inflammatory reactions. Antibodies neutralizing IL-6 or its receptor have been developed for therapy of autoimmune and chronic non-renal inflammatory diseases. Small molecule inhibitors of Janus kinases acting downstream of the IL-6 receptor, as well as recombinant soluble glycoprotein 130 variants suppressing the IL-6 trans-signaling add to the available therapeutic options. Animal data and accumulating clinical experience strongly suggest that suppression of IL-6 signaling pathways bears therapeutic potential in acute and chronic kidney diseases. The present work analyses the renoprotective potential of clinically relevant IL-6 signaling inhibitors in acute kidney injury, chronic kidney disease, and kidney transplantation with focus on current achievements and future prospects.

    Keywords: Acute Kidney Injury, Chronic Kidney Disease, Inflammation, Anti-cytokine therapy, Kidney Transplantation, Trans-signaling

    Received: 26 Sep 2024; Accepted: 08 Nov 2024.

    Copyright: © 2024 Gubernatorova, Samsonov, Drutskaya, Lebedeva, Bukhanova, Materenchuk and Mutig. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Katerina O. Gubernatorova, Engelhardt Institute of Molecular Biology (RAS), Moscow, Russia
    Kerim Mutig, Department of Pharmacology, Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University, Moscow, Russia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.