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Woxholt, Sindre; Ueland, T; Aukrust, Pål; Anstensrud, Anne Kristine; Broch, Kaspar; Tøllefsen, Ingvild Maria; Ryan, Liv; Bendz, Bjørn; Hopp, Einar; Kløw, Nils-Einar; Seljeflot, Ingebjørg; Halvorsen, Bente; Dahl, Tuva B; Huse, Camilla; Andersen, Geir Øystein; Gullestad, Lars; Wiseth, Rune; Amundsen, Brage H; Damas, Jan Kristian; Kleveland, Ola

Cytokine pattern in patients with ST-elevation myocardial infarction treated with the interleukin-6 receptor antagonist tocilizumab

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  • Media type: E-Article
  • Title: Cytokine pattern in patients with ST-elevation myocardial infarction treated with the interleukin-6 receptor antagonist tocilizumab
  • Contributor: Woxholt, Sindre; Ueland, T; Aukrust, Pål; Anstensrud, Anne Kristine; Broch, Kaspar; Tøllefsen, Ingvild Maria; Ryan, Liv; Bendz, Bjørn; Hopp, Einar; Kløw, Nils-Einar; Seljeflot, Ingebjørg; Halvorsen, Bente; Dahl, Tuva B; Huse, Camilla; Andersen, Geir Øystein; Gullestad, Lars; Wiseth, Rune; Amundsen, Brage H; Damas, Jan Kristian; Kleveland, Ola
  • imprint: BMJ, 2023
  • Published in: Open Heart
  • Language: English
  • DOI: 10.1136/openhrt-2023-002301
  • ISSN: 2053-3624
  • Origination:
  • Footnote:
  • Description: <jats:sec><jats:title>Background</jats:title><jats:p>Tocilizumab improves myocardial salvage index (MSI) in patients with ST-elevation myocardial infarction (STEMI), but its mechanisms of action are unclear. Here, we explored how cytokines were affected by tocilizumab and their correlations with neutrophils, C-reactive protein (CRP), troponin T, MSI and infarct size.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>STEMI patients were randomised to receive a single dose of 280 mg tocilizumab (n=101) or placebo (n=98) before percutaneous coronary intervention. Blood samples were collected before infusion of tocilizumab or placebo at baseline, during follow-up at 24–36, 72–168 hours, 3 and 6 months. 27 cytokines were analysed using a multiplex cytokine assay. Cardiac MRI was performed during hospitalisation and 6 months.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Repeated measures analysis of variance showed significant (p&lt;0.001) between-group difference in changes for IL-6, IL-8 and IL-1ra due to an increase in the tocilizumab group during hospitalisation. IL-6 and IL-8 correlated to neutrophils in the placebo group (r=0.73, 0.68, respectively), which was attenuated in the tocilizumab group (r=0.28, 0.27, respectively). A similar pattern was seen for MSI and IL-6 and IL-8 in the placebo group (r=−0.29, –0.25, respectively) in patients presenting ≤3 hours from symptom onset, which was attenuated in the tocilizumab group (r=−0.09,–0.14, respectively).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Tocilizumab increases IL-6, IL-8 and IL-1ra in STEMI. IL-6 and IL-8 show correlations to neutrophils/CRP and markers of cardiac injury in the placebo group that was attenuated in the tocilizumab group. This may suggest a beneficial effect of tocilizumab on the ischaemia-reperfusion injury in STEMI patients.</jats:p></jats:sec><jats:sec><jats:title>Trial registration number</jats:title><jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT03004703">NCT03004703</jats:ext-link>.</jats:p></jats:sec>
  • Access State: Open Access