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Eur J Pharmacol ; 925: 174998, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35533739

RESUMO

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.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Agentes de Imunomodulação , Imunossupressores , Inflamação , Interleucina-1beta , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Colchicina/farmacologia , Colchicina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Etanercepte/farmacologia , Etanercepte/uso terapêutico , Humanos , Hidroxicloroquina/farmacologia , Hidroxicloroquina/uso terapêutico , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/uso terapêutico , Terapia de Imunossupressão , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Inflamação/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Interleucina-1/antagonistas & inibidores , Interleucina-1beta/antagonistas & inibidores , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Sulfassalazina/farmacologia , Sulfassalazina/uso terapêutico
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