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

      Woxholt, Sindre; Ueland, Thor; 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 Børresdatter; Huse, Camilla; Andersen, Geir Øystein; Gullestad, Lars; Wiseth, Rune; Amundsen, Brage H.; Damås, Jan Kristian; Kleveland, Ola (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-08-17)
      Background - 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.<p> <p>Methods - STEMI patients were randomised to receive a single ...
    • IL-6 receptor inhibition by tocilizumab attenuated expression of C5a receptor 1 and 2 in non-ST-elevation myocardial infarction 

      Orrem, Hilde Lang; Nilsson, Per; Pischke, Søren Erik; Kleveland, Ola; Yndestad, Arne; Ekholt, Karin; Damås, Jan Kristian; Espevik, Terje; Bendz, Bjørn; Halvorsen, Bente; Gregersen, Ida; Wiseth, Rune; Andersen, Geir Øystein; Ueland, Thor; Gullestad, Lars; Aukrust, Pål; Barratt-Due, Andreas; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-09-12)
      <p><i>Background</i>: Elevated interleukin-6 (IL-6) and complement activation are associated with detrimental effects of inflammation in coronary artery disease (CAD). The complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the IL-6 receptor (IL-6R)-antagonist tocilizumab on the expression of the ...
    • Interleukin-6 inhibition in ST-elevation myocardial infarction: Immune cell profile in the randomised ASSAIL-MI trial 

      Huse, Camilla; Anstensrud, Anne Kristine; Michelsen, Annika Elisabet; Ueland, Thor; Broch, Kaspar; Woxholt, Sindre; Yang, Kuan; Sharma, Kapil Kishore; Tøllefsen, Ingvild Maria; Bendz, Bjørn; Amundsen, Brage H.; Damås, Jan Kristian; Berg, Erlend Sturle; Bjørkelund, Elisabeth; Quiles-Jiménez, Ana M T; Bjerkeli, Vigdis; Bendz, Christina; Kleveland, Ola; Stensæth, Knut Haakon; Opdahl, Anders; Kløw, Nils-Einar; Andersen, Geir Øystein; Wiseth, Rune; Halvorsen, Bente; Gullestad, Lars; Seljeflot, Ingebjørg; Aukrust, Pål; Osnes, Liv T. N.; Dahl, Tuva Børresdatter (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-04-30)
      Background We recently showed that interleukin (IL)-6 inhibition by tocilizumab improves myocardial salvage in ST-elevation myocardial infarction (STEMI). However, the mechanisms for this effect are not clear.<p> <p>Methods In this exploratory sub-study of the ASSAIL-MI trial, we examined leukocyte differential counts and their relation to myocardial salvage and peak troponin T (TnT) in STEMI ...
    • Interleukin-6 receptor inhibition with tocilizumab induces a selective and substantial increase in plasma IP-10 and MIP-1β in non-ST-elevation myocardial infarction 

      Kleveland, Ola; Ueland, Thor; Kunszt, Gabor; Bratlie, Marte; Yndestad, Arne; Broch, Kaspar; Holte, Espen; Ryan, Liv; Amundsen, Brage H.; Bendz, Bjørn; Aakhus, Svend; Espevik, Terje; Halvorsen, Bente; Mollnes, Tom Eirik; Wiseth, Rune; Gullestad, Lars; Aukrust, Pål; Damås, Jan Kristian (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-06-29)
      <p><i>Aim</i>: To evaluate the effect of interleukin-6 inhibition with tocilizumab on the cytokine network in patients with acute non-ST-elevation myocardial infarction (NSTEMI).</p> <p><i>Methods</i>: 117 patients with acute NSTEMI were randomised to an intravenous infusion of 280 mg tocilizumab or placebo prior to coronary angiography. Blood samples were obtained at baseline, at 6 consecutive ...
    • Novel Insights Into the Effects of Interleukin 6 Antagonism in Non-ST-Segment-Elevation Myocardial Infarction Employing the SOMAscan Proteomics Platform 

      George, Marc J; Kleveland, Ola; Garcia-Hernandez, Jorge; Palmen, Jutta; Lovering, Ruth; Wiseth, Rune; Aukrust, Pål; Engmann, Jorgen; Damås, Jan Kristian; Hingorani, Aroon D; Gullestad, Lars; Casas, Juan P; Ueland, Thor (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-06-09)
      <p>Background: Interleukin 6 concentration is associated with myocardial injury, heart failure, and mortality after myocardial infarction. In the Norwegian tocilizumab non-ST-segment-elevation myocardial infarction trial, the first randomized trial of interleukin 6 blockade in myocardial infarction, concentration of both C-reactive protein and troponin T were reduced in the active treatment arm. In ...
    • Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction 

      Broch, Kaspar; Anstensrud, Anne Kristine; Woxholt, Sindre; Sharma, Kapil Kishore; Tøllefsen, Ingvild Maria; Bendz, Bjørn; Aakhus, Svend; Ueland, Thor; Amundsen, Brage H.; Damås, Jan Kristian; Berg, Erlend; Bjørkelund, Elisabeth; Bendz, Christina; Hopp, Einar; Kleveland, Ola; Stensæth, Knut Haakon; Opdahl, Anders; Kløw, Nils-Einar; Seljeflot, Ingebjørg; Andersen, Geir Øystein; Wiseth, Rune; Aukrust, Pål; Gullestad, Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-04-12)
      <p><i>Background - </i>Prompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response. <p><i>Objectives - </i>This study sought ...
    • Rationale for the ASSAIL-MI-trial: a randomised controlled trial designed to assess the effect of tocilizumab on myocardial salvage in patients with acute ST-elevation myocardial infarction (STEMI) 

      Anstensrud, Anne Kristine; Voxholt, Sindre; Sharma, Kapil; Broch, Kaspar; Bendz, Bjørn; Aakhus, Svend; Ueland, Thor; Amundsen, Brage H.; Damås, Jan Kristian; Hopp, Einar; Kleveland, Ola; Stensæth, Knut Haakon; Opdahl, Anders; Kløw, Nils-Einar; Seljeflot, Ingebjørg; Andersen, Geir Øystein; Wiseth, Rune; Aukrust, Pål; Gullestad, Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-10-15)
      <i>Introduction</i>: Interleukin-6 (IL-6) may be involved in ischaemia-reperfusion injury and myocardial remodelling after myocardial infarction (MI). We have recently shown that IL-6 inhibition by tocilizumab attenuates systemic inflammation and troponin T-release in patients with acute non-ST elevation MI (NSTEMI). Experimental studies suggest that IL-6 inhibition can limit infarct size through ...
    • Serum PCSK9 is modified by interleukin-6 receptor antagonism in patients with hypercholesterolaemia following non-ST-elevation myocardial infarction 

      Ueland, Thor; Kleveland, Ola; Michelsen, Annika; Wiseth, Rune; Damås, Jan Kristian; Aukrust, Pål; Gullestad, Lars; Halvorsen, Bente; Yndestad, Arne (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-09-18)
      <p><i>Objective</i>: It is unclear if activation of inflammatory pathways regulates proprotein convertase subtilisin-kexin type 9 (PCSK9) levels.</p> <p><i>Approach</i>: We evaluated (1) the temporal course of serum PCSK9 during hospitalisation following acute coronary syndrome and associations with markers of inflammation (leucocyte counts, interleukin (IL)-6, C-reactive protein) and lipid levels ...
    • Tocilizumab increases citrullinated histone 3 in non-ST segment elevation myocardial infarction 

      Helseth, Ragnhild; Kleveland, Ola; Ueland, Thor; Wiseth, Rune; Damås, Jan Kristian; Broch, Kaspar; Michelsen, Annika Elisabet; Bendz, Bjørn; Gullestad, Lars; Aukrust, Pål; Seljeflot, Ingebjørg (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-05-10)
      Objective: Beyond reducing inflammation and troponin T (TnT) release, the interleukin-6 receptor antagonist tocilizumab reduces neutrophil counts in patients with non-ST segment elevation myocardial infarction (NSTEMI). It is unclear if this is related to formation of neutrophil extracellular traps (NETs), carrying inflammatory and thrombotic properties.<p> <p>Methods - In a placebo-controlled ...