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

TY - JOUR

T1 - Immunomodulatory and immunosuppressive therapies in cardiovascular disease and type 2 diabetes mellitus

T2 - A bedside-to-bench approach

AU - Mikkelsen, Rasmus R

AU - Hundahl, Malthe P

AU - Torp, Christopher K

AU - Rodríguez-Carrio, Javier

AU - Kjolby, Mads

AU - Bruun, Jens M

AU - Kragstrup, Tue W

N1 - Copyright © 2022. Published by Elsevier B.V.

PY - 2022/6

Y1 - 2022/6

N2 - 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.

AB - 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.

KW - Animals

KW - Cardiovascular Diseases/drug therapy

KW - Colchicine

KW - Diabetes Mellitus, Type 2/complications

KW - Etanercept/pharmacology

KW - Humans

KW - Hydroxychloroquine/therapeutic use

KW - Immunosuppression Therapy

KW - Inflammation/chemically induced

KW - Interleukin 1 Receptor Antagonist Protein/therapeutic use

KW - Methotrexate/therapeutic use

KW - Sulfasalazine/therapeutic use

KW - Hydroxychloroquine/pharmacology

KW - Immunomodulating Agents/pharmacology

KW - Sulfasalazine/pharmacology

KW - Colchicine/pharmacology

KW - Interleukin-1/antagonists & inhibitors

KW - Diabetes Mellitus, Type 2/drug therapy

KW - Interleukin 1 Receptor Antagonist Protein/pharmacology

KW - Interleukin-1beta/antagonists & inhibitors

KW - Antibodies, Monoclonal, Humanized/pharmacology

KW - Immunosuppressive Agents/pharmacology

KW - Inflammation/drug therapy

KW - Methotrexate/pharmacology

U2 - 10.1016/j.ejphar.2022.174998

DO - 10.1016/j.ejphar.2022.174998

M3 - Review

C2 - 35533739

SN - 0014-2999

VL - 925

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

M1 - 174998

ER -