Interleukin-6 and tumor necrosis factor-α in osteoimmunology: Aging, and anticytokine therapies

doi:10.5528/wjtm.122119

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World Journal of Translational Medicine

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2220-6132

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Transl Med. Sep 28, 2026; 12(3): 122119
Published online Sep 28, 2026. doi: 10.5528/wjtm.122119

Interleukin-6 and tumor necrosis factor-α in osteoimmunology: Aging, and anticytokine therapies

Arunagiri Gunasekar, Naveen Jeyaraman, Sneha Babu Chitra, Vathani Yudakar, Sanjeevi Bharadwaj, Sathish Muthu, Madhan Jeyaraman

Arunagiri Gunasekar, Sneha Babu Chitra, Department of Orthopaedics, Government Medical College and Hospital, Thiruvallur 602001, Tamil Nadu, India

Naveen Jeyaraman, Madhan Jeyaraman, Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India

Naveen Jeyaraman, Sathish Muthu, Madhan Jeyaraman, Department of Regenerative Medicine, Agathisha Institute of Stemcell and Regenerative Medicine, Chennai 600030, Tamil Nadu, India

Naveen Jeyaraman, Sathish Muthu, Madhan Jeyaraman, Department of Orthopaedics, Orthopaedic Research Group, Coimbatore 641045, Tamil Nadu, India

Vathani Yudakar, Department of Orthopaedics, ESIC Medical College & PGIMSR, Chennai 600078, Tamil Nadu, India

Sanjeevi Bharadwaj, Department of Trauma and Orthopaedics, Wye Valley NHS Trust, Hereford HR1 2BN, Herefordshire, United Kingdom

Sathish Muthu, Central Research Laboratory, Meenakshi Medical College Hospital and Research Institute, Meenakshi Academy of Higher Education and Research, Kanchipuram 631552, Tamil Nadu, India

Co-first authors: Arunagiri Gunasekar and Naveen Jeyaraman.

Author contributions: Jeyaraman N, Bharadwaj S, and Jeyaraman M designed the research; Chitra SB, Gunasekar A, Jeyaraman N, Bharadwaj S, and Yadukar V analyzed the articles for performing review and wrote the manuscript; Muthu S and Jeyaraman M finalized the manuscript.

AI contribution statement: AI has not been utilized in developing the manuscript.

Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.

Corresponding author: Madhan Jeyaraman, MD, PhD, Associate Professor, Researcher, Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Velappanchavadi, Chennai 600077, Tamil Nadu, India. madhanjeyaraman@gmail.com

Received: April 10, 2026
Revised: July 20, 2026
Accepted: August 18, 2026
Published online: September 28, 2026
Processing time: 146 Days and 12.6 Hours

Core Tip

Core Tip: Interleukin (IL)-6 and tumor necrosis factor (TNF)-α are important cytokines that have been implicated in the pathogenesis of bone loss by means of an imbalance of receptor activator of nuclear factor (NF)-κB ligand/osteoprotegerin, NF-κB activation, and osteoclast encouragement. They are aggravated by inflammatory bone diseases and osteoporosis caused by inflammaging and senescence-associated secretory phenotype. Their crosstalk promotes bone resorption by dysregulating immune cells. Anti-TNF-α and anti-IL-6 treatments normalize bone homeostasis, and observational data suggest a lower reduction in fracture occurrence, an estimate that should be interpreted cautiously given its non-randomized basis. These novel methods include senolytics, Janus kinase, and cytokine-based precision medicine.