Skip to main content
SpringerLink
Log in

Satralizumab, Novel Interleukine-6 Inhibitor for Preventing Descending Thoracic Aorta Aneurysm Development

  • Original Article
  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Background

Descending thoracic aorta aneurysm (dTAA) has increasing incidence and, if left untreated, could lead to death. There is not any study of satralizumab treatment for preventing dTAA formation and progression.

Materials and Methods

Forty male 10-week-old Rattus norvegicus were enrolled in the experiment. They were divided into four equal groups: dTAA treated with saline (dTAA-P) and dTAA treated with satralizumab (dTAA-S). One of the control groups was treated with saline (C-P), and the other was treated with satralizumab (C-S). Satralizumab and saline were used once every 2 weeks, subcutaneously 120 mg for 4 weeks. dTA diameter was measured at days 0, 3, 7, 14, 21, and 28.

Results

IL-6 level was measured on the 7th day that showed significantly increased IL-6 serum level in dTAA-P rats compared to C-P. Maximal dTA diameter (%MAD) was obtained at day 14, which was scientifically matched to the aorta aneurysm definition (>50% increase in diameter). From the seventh day, a significant difference in %MAD was observed between dTAA-P and dTAA-S groups. However, the %MAD of these two groups was significantly higher than control groups till the end of the 28th day.

Conclusion

Using an IL-6 inhibitor agent to prevent dTAA formation and progression showed promising results. It suggests that using the IL-6 inhibitors in susceptible persons can be considered a lifesaving therapeutic approach.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

All available data will be provided upon asking by email from Dr. Amir Hossein Heydari (email: amhohe@gmail.com).

Abbreviations

dTAA:

Descending thoracic aorta aneurysm

dTAA-P:

dTAA treated with saline

dTAA-S:

dTAA treated with satralizumab

C-P:

Control group treated with saline

C-S:

Control group treated with satralizumab

IL-6:

Interleukine-6

TAA:

Thoracic aorta aneurysms

dTA:

Descending thoracic aorta

STZ:

Satralizumab

References

  1. Faiza Z, Sharman T. Thoracic aorta aneurysm. StatPearls [Internet]. 2021.

  2. Yaghoubi M, Jafari S, Sajedi B, Gohari S, Akbarieh S, Heydari AH, et al. Comparison of fenofibrate and pioglitazone effects on patients with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol. 2017;29(12):1385–8.

    Article  CAS  PubMed  Google Scholar 

  3. Geisbüsch S, Kuehnl A, Salvermoser M, Reutersberg B, Trenner M, Eckstein H-H. Increasing incidence of thoracic aortic aneurysm repair in Germany in the endovascular era: secondary data analysis of the nationwide German DRG microdata. Eur J Vasc Endovasc Surg. 2019;57(4):499–509.

    Article  PubMed  Google Scholar 

  4. Sadeghi A, Rad ZA, Sajedi B, Heydari AH, Akbarieh S, Jafari B. Effect of weight losing on the clinical status improvement of patients with knee osteoarthritis. Reumatologia clinica. 2019;15(2):73–6.

    Article  PubMed  Google Scholar 

  5. Yagi H, Nishigori M, Murakami Y, Osaki T, Muto S, Iba Y, et al. Discovery of novel biomarkers for atherosclerotic aortic aneurysm through proteomics-based assessment of disease progression. Sci Rep. 2020;10(1):1–12.

    Google Scholar 

  6. Rad ZA, Sajedi B, Akbarieh S, Heydari AH, Ali SB, Mojdehi AM. A case report of isolated thrombocytopenia induced by brucellosis. Asian Pacific Journal of Tropical Disease. 2017;7(3):181–2.

    Article  Google Scholar 

  7. Fukui T. Management of acute aortic dissection and thoracic aortic rupture. J Intensive Care. 2018;6(1):1–8.

    Article  Google Scholar 

  8. Farahani B, Skandari R, Abbasi MA, Aghalou S, Gohari S, Heydari AH, et al. The association between myocardial perfusion scan and electrocardiographic findings among patients with myocardial ischemia. Int J Cardiovasc Pract. 2017;2(1):17–20.

    Article  Google Scholar 

  9. Pisano C, Balistreri CR, Ricasoli A, Ruvolo G. Cardiovascular disease in ageing: an overview on thoracic aortic aneurysm as an emerging inflammatory disease. Mediat Inflamm. 2017;2017.

  10. Fujita D, Preiss L, Aizawa K, Asch F, Eagle K, Suzuki T, et al. Circulating interleukin-6 (IL-6) levels are associated with aortic dimensions in genetic aortic conditions. PLoS One. 2019;14(3):e0214084.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sadeghi A, Rad Z, Sajedi B, Heydari A, Akbarieh S, Jafari B. Effect of weight losing on the improving clinical statement of patients with knee osteoarthritis. Reumatologia clinica. 2017.

  12. Yamamura T, Kleiter I, Fujihara K, Palace J, Greenberg B, Zakrzewska-Pniewska B, et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381(22):2114–24.

    Article  CAS  PubMed  Google Scholar 

  13. Tyerman Z, Dahl J, Shannon A, Johnston WF, Pope NH, Lu G, et al. Murine surgical model of topical elastase induced descending thoracic aortic aneurysm. JoVE (Journal of Visualized Experiments). 2019;150:e60105.

    Google Scholar 

  14. Heo Y-A. Satralizumab: first approval. Drugs. 2020:1-6.

  15. Yamamura T, Kleiter I, Fujihara K, Palace J, Greenberg B, Zakrzewska-Pniewska B, et al. Efficacy of satralizumab (SA237) in subgroups of patients in SAkuraSky: a phase III double-blind, placebo-controlled, add-on study in patients with neuromyelitis optica spectrum disorder (NMOSD)(S43. 008). AAN Enterprises; 2019.

  16. Paige E, Clément M, Lareyre F, Sweeting M, Raffort J, Grenier C, et al. Interleukin-6 receptor signaling and abdominal aortic aneurysm growth rates. Circulation: Genomic and Precision Medicine. 2019;12(2):e002413.

    CAS  PubMed  Google Scholar 

  17. Dawson J, Cockerill GW, Choke E, Belli A-M, Loftus I, Thompson MM. Aortic aneurysms secrete interleukin-6 into the circulation. J Vasc Surg. 2007;45(2):350–6.

    Article  PubMed  Google Scholar 

  18. Johnston WF, Salmon M, Pope NH, Meher A, Su G, Stone ML, et al. Inhibition of interleukin-1β decreases aneurysm formation and progression in a novel model of thoracic aortic aneurysms. Circulation. 2014;130(11_suppl_1):S51-S9.

  19. Nishihara M, Aoki H, Ohno S, Furusho A, Hirakata S, Nishida N, et al. The role of IL-6 in pathogenesis of abdominal aortic aneurysm in mice. PLoS One. 2017;12(10):e0185923.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Greenberg B, De Seze J, Fox E, Saiz A, Yamamura T, Marcillat C, et al. Safety of satralizumab based on pooled data from phase 3 studies in patients with neuromyelitis optica spectrum disorder (NMOSD)(1281). AAN Enterprises; 2020.

  21. Gao Y, Zhang B, Yang J. Satralizumab for the treatment of neuromyelitis optica spectrum disorders. Annals of Pharmacotherapy. 2020:1060028020976669.

  22. Rosso M, Saxena S, Chitnis T. Targeting IL-6 receptor in the treatment of neuromyelitis optica spectrum: a review of emerging treatment options. Expert Rev Neurother. 2020;20(5):509–16.

    Article  CAS  PubMed  Google Scholar 

  23. Ogata A, Kato Y, Higa S, Yoshizaki K. IL-6 inhibitor for the treatment of rheumatoid arthritis: a comprehensive review. Mod Rheumatol. 2019;29(2):258–67.

    Article  CAS  PubMed  Google Scholar 

  24. Duchow A, Bellmann-Strobl J. Satralizumab in the treatment of neuromyelitis optica spectrum disorder. Neurodegenerative Disease Management. 2021;11(1):49–59.

    Article  PubMed  Google Scholar 

Download references

Code Availability

Not applicable

Funding

The first author paid all costs.

Author information

Authors and Affiliations

  1. School of Medicine, Zanjan University of Medical Science, Zanjan, Iran

    Amir Hossein Heydari

  2. Shahid Beheshti Hospital, Zanjan University of Medical Science, Zanjan, Iran

    Sophia Heydari

  3. Department of Electrical Engineering, Henry Samueli School of Engineering, University of California, Los Angeles, CA, USA

    Mohammad Esmaeil Heidari

Authors
  1. Amir Hossein Heydari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sophia Heydari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammad Esmaeil Heidari
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AHH is taking full responsibility for all data; AHH contributed to study design, and AHH and SH conducted laboratorial procedures. AHH and MEH contributed to data analysis. AHH, SH, and MEH contributed to graphical designs. AHH, SH, and MEH wrote the draft of the manuscript. AHH and MEH wrote the final version of the manuscript.

Corresponding author

Correspondence to Amir Hossein Heydari.

Ethics declarations

Ethics Approval

Mentioned in materials and methods.

Consent for Publication

Not applicable

Consent for Participation

Not applicable

Conflict of Interests

The authors declare no competing interests.

Research in Context

What are already known in this context?

• The most definitive treatment for TAA is an open aortic repair with a mortality rate of up to 10% within 1 month after the operation.

• Today there is a lack of knowledge about TAA pathology, so specific drugs for the TAA have not been proposed yet.

• Using satralizumab as an IL-6 receptor blocker was proven safe and effective in neuromyelitis.

What is the main question?

• Is satralizumab able to prevent the beginning and progression of thoracic aorta aneurysm?

What are the new findings?

• Antagonizing the IL-6 receptor by satralizumab attenuated the formation of the dTAA and decreased the growth rate of dTAA.

What are the impacts on clinical practice?

• Satralizumab can be considered a potential anti-aneurysm agent in predisposed patients to prevent the emerging and development of the descending thoracic aorta aneurysm.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(XLSX 10 kb)

ESM 2

(DOCX 75 kb)

ESM 3

(DOCX 52 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Heydari, A.H., Heydari, S. & Heidari, M.E. Satralizumab, Novel Interleukine-6 Inhibitor for Preventing Descending Thoracic Aorta Aneurysm Development. Cardiovasc Drugs Ther 37, 239–244 (2023). https://doi.org/10.1007/s10557-021-07294-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-021-07294-9

Keywords

Search

Navigation