Ivermectin — New Hope for Arthritis

Ivermectin — New Hope for Arthritis

Inflammation Is at the Core of COVID and Arthritis Symptoms

Inflammation is the body’s protective response to injury or infection, but sometimes it gets out of control, causing problems in diseases like COVID-19, rheumatoid arthritis (RA), and osteoarthritis (OA). Scientists have discovered that these three diseases trigger similar patterns inside the body, leading to swelling, pain, and tissue damage. (1,2,3,4,5,6,7)

Shared Inflammatory Pathways

When someone has COVID-19, RA, or OA, their immune system releases chemicals known as cytokines. Cytokines are signaling proteins the body uses to call immune cells to fight infection or heal injury. In these conditions, cytokines become overly active and rally too many immune cells, leading to inflammation that can hurt rather than heal. (8)

The Inflammatory Cytokine Triad: TNF-α, IL-6, and IL-1β

  • Tumor Necrosis Factor-alpha (TNF-α): A powerful chemical messenger that signals for inflammation. When released in large amounts, it can cause redness, swelling, and pain. (8,9)
  • Interleukin-6 (IL-6): Directs many immune responses, including fever and the production of protective proteins. Excess IL-6 often results in more inflammation and chronic illness. (9)
  • Interleukin-1 beta (IL-1β): Like TNF-α and IL-6, IL-1β ramps up inflammation and contributes to tissue damage. High levels are common in chronic diseases. (8,9)

This triad appears at elevated levels in COVID-19 (as part of the “cytokine storm”), RA (causing joint swelling and damage), and OA (resulting in chronic joint pain and breakdown). (7,10)

Signaling Pathways in Common

  • NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells): Acts as a master switch inside cells. Overactivation leads to ongoing inflammation and tissue injury. (11,12)
  • MAPK (Mitogen-Activated Protein Kinase): A chain-reaction system spreading inflammation signals throughout the cell. Branches like p38, ERK1/2, and JNK amplify cytokine production. (13,14)
  • JAK/STAT Pathway: Proteins that transmit messages from cytokines like IL-6 into the cell nucleus, triggering more inflammation. JAK inhibitors can block this step to control inflammation in COVID-19 and RA. (15)

Ivermectin’s Anti-Inflammatory Effects

Initially developed to kill parasites, studies suggest ivermectin helps modulate inflammation as well:

  • NF-κB Pathway Inhibition: Blocks the master switch, reducing swelling and tissue damage. (19,20)
  • Direct Cytokine Suppression: Lowers TNF-α, IL-6, and IL-1β levels, limiting harmful inflammation. (18,21)
  • MAPK Pathway Modulation: Prevents the inflammatory chain reaction within cells. (22)
  • JAK/STAT Pathway Interference: Slows the JAK/STAT proteins, putting the brake on chronic inflammation. Beneficial in COVID-19 and RA. (22)
  • Novel Integrin-Based Mechanism: May block another “doorway” that inflammatory messengers use to exacerbate tissue damage. (23)

Because COVID-19, RA, and OA share similar internal signaling pathways that drive inflammation, medications like ivermectin that block these steps could potentially help treat all three. While ivermectin is not officially approved for these uses, research suggests it may one day contribute to better therapies for multiple inflammatory diseases.

References

  1. Chow, Y. Y., & Chin, K. Y. (2020). The role of inflammation in the pathogenesis of osteoarthritis. Mediators of Inflammation, 2020, Article 8293921. https://doi.org/10.1155/2020/8293921
  2. Abcam. (n.d.). Cytokine storm in COVID- pathway. Abcam. Retrieved October 1, 2025, from https://www.abcam.com/en-us/technical-resources/pathways/cytokine-storm-in-covid-19-pathway
  3. Yang, L., Xie, X., Tu, Z., Fu, J., Xu, D., & Zhou, Y. (2021). The signal pathways and treatment of cytokine storm in COVID-19. Signal Transduction and Targeted Therapy, 6, 255. https://doi.org/10.1038/s41392-021-00679-0
  4. Cell Signaling Technology. (n.d.). Rheumatoid arthritis pathogenesis signaling pathway. Retrieved October 1, 2025, from https://www.cellsignal.com/pathways/rheumatoid-arthritis
  5. Zhang, Y., Fu, Y., Wang, Y., & Deng, W. (2023). Osteoarthritis: Pathogenic signaling pathways and therapeutic targets. Signal Transduction and Targeted Therapy, 8, Article 169. https://doi.org/10.1038/s41392-023-01330-w
  6. Li, M., Wang, Y., Lin, C., & Liu, H. (2023). Signaling pathways in rheumatoid arthritis: Implications for targeted therapy. Signal Transduction and Targeted Therapy, 8, Article 170. https://doi.org/10.1038/s41392-023-01331-9
  7. Thermo Fisher Scientific. (n.d.). Pro-inflammatory cytokines overview. https://www.thermofisher.com/.../proinflammatory-cytokines-overview.html
  8. Zhao, Y., Liu, J., Yang, C., Zheng, W., & Zhu, J. (2024). Cytokine network in inflammatory diseases: Current advances and future perspectives. Frontiers in Immunology, 15, 1330386. Frontiers in Immunology
  9. News Medical. (2021, November 18). Triad of cytokines associated with long COVID. https://www.news-medical.net/.../Triad-of-cytokines-associated-with-long-COVID.aspx
  10. Dinarello, C. A. (2010). Proinflammatory cytokines. Chest, 118(2), 503–508. https://pmc.ncbi.nlm.nih.gov/articles/PMC2882124/
  11. Luo, Y., & Zheng, S. (2017). Signaling cross talk between TGF-β/Smad and other signaling pathways. Signal Transduction and Targeted Therapy, 2(1), 17023. https://www.nature.com/articles/sigtrans201723
  12. Assay Genie. (n.d.). MAPK signaling and cytokines pathways. https://www.assaygenie.com/.../mapk-signaling-cytokines-pathways
  13. Chen, L., & Deng, H. (2017). The molecular mechanisms of macrophage polarization and phagocytosis. International Review of Immunology, 36(6), 547–565. https://pmc.ncbi.nlm.nih.gov/articles/PMC3899974/
  14. Liu, C., Wu, J., Zhu, J., Kullak-Ublick, G. A., & Lu, Y. (2022). Pharmacological modulation of cytokines in inflammation: Mechanisms and therapeutic strategies. Frontiers in Pharmacology, 13, 1033674. Frontiers in Pharmacology
  15. Smyth, L., Williams, L., & Hays, J. (2020). The cytokine profile of COVID-19 patients. Cytokine, 136, 155264. https://pmc.ncbi.nlm.nih.gov/articles/PMC7539925/
  16. López-Collazo, E., & del Fresno, C. (2020). Pathogenesis of severe COVID-19: The interplay between the cytokine storm and immunosuppression. Cytokine & Growth Factor Reviews, 55, 1–10. https://pmc.ncbi.nlm.nih.gov/articles/PMC7476419/
  17. Subramaniam, A. V., & Chalmers, J. (2020). Cytokines and cardiovascular disease: Updating evidence and standards. Open Heart, 7(2), e001350. https://openheart.bmj.com/content/7/2/e001350
  18. Wu, D., & Yang, X. O. (2021). TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor fedratinib. Frontiers in Immunology, 12, 620492. https://pmc.ncbi.nlm.nih.gov/articles/PMC8688140/
  19. Martonik, D., Parfieniuk, E., & Szynkiewicz, M. (2020). Cytokine and chemokine patterns in COVID-19 and long COVID. Frontiers in Immunology, 11, 584706. https://pmc.ncbi.nlm.nih.gov/articles/PMC7578741/
  20. Zhang, J., & Zhang, W. (2018). Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice. Semantic Scholar. https://www.semanticscholar.org/.../Ivermectin-inhibits-LPS...
  21. Asghari, A., Ghadiri, M. K., Sayehmiri, F., et al. (2022). The immunopathological mechanisms of cytokine storm and therapeutic approaches for COVID-19. International Immunopharmacology, 112, 109155. https://pmc.ncbi.nlm.nih.gov/articles/PMC9442455/
  22. Kamal, R., & Kaur, T. (2024). Cytokines: A link between inflammation and cancer. PubMed. https://pubmed.ncbi.nlm.nih.gov/40943574/

Written by Brooke Lounsbury

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