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

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

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Cardiovascular Diseases* / drug therapy
  • Colchicine / pharmacology
  • Colchicine / therapeutic use
  • Diabetes Mellitus, Type 2* / drug therapy
  • Etanercept / pharmacology
  • Etanercept / therapeutic use
  • Humans
  • Hydroxychloroquine / pharmacology
  • Hydroxychloroquine / therapeutic use
  • Immunomodulating Agents* / pharmacology
  • Immunomodulating Agents* / therapeutic use
  • Immunosuppression Therapy
  • Immunosuppressive Agents* / pharmacology
  • Immunosuppressive Agents* / therapeutic use
  • Inflammation* / drug therapy
  • Interleukin 1 Receptor Antagonist Protein / pharmacology
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1beta* / antagonists & inhibitors
  • Methotrexate / pharmacology
  • Methotrexate / therapeutic use
  • Sulfasalazine / pharmacology
  • Sulfasalazine / therapeutic use

Substances

  • Antibodies, Monoclonal, Humanized
  • Immunomodulating Agents
  • Immunosuppressive Agents
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Interleukin-1beta
  • canakinumab
  • Sulfasalazine
  • Hydroxychloroquine
  • Etanercept
  • Colchicine
  • Methotrexate