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Eur J Pharmacol ; 925: 174998, 2022 Jun 15.
Article in English | MEDLINE | ID: mdl-35533739

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 ß-cell function in T2D. Etanercept had no effect in patients with T2D. CONCLUSION: The observed results indicate that immunosuppressive drugs specifically targeting IL-1ß 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.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Immunomodulating Agents , Immunosuppressive Agents , Inflammation , Interleukin-1beta , 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
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