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Immunomodulatory and immunosuppressive therapies in cardiovascular disease and type 2 diabetes mellitus: A bedside-to-bench approach

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  • Rasmus R Mikkelsen, Aarhus University
  • ,
  • Malthe P Hundahl, Aarhus University
  • ,
  • Christopher K Torp
  • ,
  • Javier Rodríguez-Carrio, Universidad de Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias
  • ,
  • Mads Kjolby
  • Jens M Bruun
  • Tue W Kragstrup

OBJECTIVE: To assess which immunosuppressive drugs have been investigated and proven efficacious in patients with cardiovascular disease (CVD) or type 2 diabetes (T2D) without preexisting immune mediated disorders to validate in vitro and animal model findings on low grade inflammation (bedside-to-bench).

METHODS: Clinical trials on immunosuppressive drugs in CVD or T2D were found in PubMed. Studies on patients with preexisting immune mediated inflammatory disease were excluded. A total of 19 clinical trials testing canakinumab, anakinra, methotrexate, colchicine, hydroxychloroquine, etanercept and sulfasalazine were found.

RESULTS: Canakinumab and colchicine significantly reduced the risk of CVD, whereas methotrexate did not. Sulfasalazine showed no effect on vascular function. Anakinra and hydroxychloroquine had a positive effect on glycemic control and β-cell function in T2D. Etanercept had no effect in patients with T2D.

CONCLUSION: The observed results indicate that immunosuppressive drugs specifically targeting IL-1β hold promise for dampening CVD and T2D. These findings validate in vitro and animal models showing involvement of the IL-1-axis in the pathogenesis of CVD and T2D. The use of immunosuppressive drugs targeting the chronic inflammation in these diseases could be a possible future treatment strategy as an add-on to the existing pharmacological treatment of CVD and T2D. However, potential treatment effects, adverse events and cost-effectiveness should be carefully considered with importance for drug development.

Original languageEnglish
Article number174998
JournalEuropean Journal of Pharmacology
Volume925
Number of pages10
ISSN0014-2999
DOIs
Publication statusPublished - Jun 2022

Bibliographical note

Copyright © 2022. Published by Elsevier B.V.

    Research areas

  • Animals, Cardiovascular Diseases/drug therapy, Colchicine, Diabetes Mellitus, Type 2/complications, Etanercept/pharmacology, Humans, Hydroxychloroquine/therapeutic use, Immunosuppression Therapy, Inflammation/chemically induced, Interleukin 1 Receptor Antagonist Protein/therapeutic use, Methotrexate/therapeutic use, Sulfasalazine/therapeutic use

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