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Review
. 2022 Jun 15:925:174998.
doi: 10.1016/j.ejphar.2022.174998. Epub 2022 May 6.

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

Affiliations

Affiliations

  • 1 Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • 2 Area of Immunology, Department of Functional Biology, Universidad de Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Asturias, Spain.
  • 3 Department of Biomedicine, Aarhus University, Aarhus, Denmark; Steno Diabetes Centre Aarhus, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.
  • 4 Steno Diabetes Centre Aarhus, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, University of Aarhus, Aarhus C, Denmark.
  • 5 Department of Biomedicine, Aarhus University, Aarhus, Denmark; Diagnostic Center, Silkeborg Regional Hospital, Silkeborg, Denmark. Electronic address: kragstrup@biomed.au.dk.
Free article
Review

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

Rasmus R Mikkelsen et al. Eur J Pharmacol. .
Free article
. 2022 Jun 15:925:174998.
doi: 10.1016/j.ejphar.2022.174998. Epub 2022 May 6.

Affiliations

  • 1 Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • 2 Area of Immunology, Department of Functional Biology, Universidad de Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Asturias, Spain.
  • 3 Department of Biomedicine, Aarhus University, Aarhus, Denmark; Steno Diabetes Centre Aarhus, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark.
  • 4 Steno Diabetes Centre Aarhus, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, University of Aarhus, Aarhus C, Denmark.
  • 5 Department of Biomedicine, Aarhus University, Aarhus, Denmark; Diagnostic Center, Silkeborg Regional Hospital, Silkeborg, Denmark. Electronic address: kragstrup@biomed.au.dk.

Abstract

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.

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