Ola Kleveland1, Thor Ueland2, Gabor Kunszt3, Marte Bratlie4, Arne Yndestad5, Kaspar Broch6, Espen Holte7, Liv Ryan8, Brage H Amundsen7, Bjørn Bendz9, Svend Aakhus7, Terje Espevik8, Bente Halvorsen10, Tom E Mollnes11, Rune Wiseth7, Lars Gullestad12, Pål Aukrust13, Jan Kristian Damås8. 1. Clinic of Cardiology, St. Olavs Hospital, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology NTNU, Trondheim, Norway. Electronic address: ola.kleveland@stolav.no. 2. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; Institute of Clinical Medicine, University of Oslo, Norway; K.G. Jebsen Centre of Inflammatory Research, University of Oslo, Norway; K.G. Jebsen Cardiac Research Centre, University of Oslo, Norway. 3. Institute of Clinical Medicine, University of Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway. 4. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; Institute of Clinical Medicine, University of Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway. 5. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; Institute of Clinical Medicine, University of Oslo, Norway; K.G. Jebsen Centre of Inflammatory Research, University of Oslo, Norway; Centre for Heart Failure Research, University of Oslo, Norway. 6. K.G. Jebsen Cardiac Research Centre, University of Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway. 7. Clinic of Cardiology, St. Olavs Hospital, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology NTNU, Trondheim, Norway. 8. Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology NTNU, Trondheim, Norway. 9. Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway. 10. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway. 11. Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology NTNU, Trondheim, Norway; K.G. Jebsen Centre of Inflammatory Research, University of Oslo, Norway; Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway; Research laboratory, Nordland Hospital, Bodø, Norway; Faculty of Health Sciences, K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway. 12. Institute of Clinical Medicine, University of Oslo, Norway; K.G. Jebsen Cardiac Research Centre, University of Oslo, Norway; Centre for Heart Failure Research, University of Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway. 13. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; Institute of Clinical Medicine, University of Oslo, Norway; K.G. Jebsen Centre of Inflammatory Research, University of Oslo, Norway.
Abstract
AIM: To evaluate the effect of interleukin-6 inhibition with tocilizumab on the cytokine network in patients with acute non-ST-elevation myocardial infarction (NSTEMI). METHODS: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 points in time during hospitalisation, and at follow-up after 3 and 6 months. Cytokines (n = 27) were analysed with a multiplex cytokine assay. RESULTS: Using a mixed between-within subjects analysis of variance, we observed a significant (p < 0.001) between-group difference in changes for interferon gamma-inducible protein (IP-10) and macrophage inflammatory protein-1β (MIP-1β), due to significant increases in the tocilizumab group during hospitalisation (i.e., IP-10 median change from baseline during hospitalisation (mΔ), placebo: 3 (-60, 68) pg/ml vs tocilizumab: 209 (69, 335) pg/ml; MIP-1β mΔ, placebo: 5 (-2, 12) pg/ml vs tocilizumab: 39 (24, 63) pg/ml). MIP-1β was inversely correlated to troponin T (r = -0.28, p < 0.05) and neutrophils (r = -0.32, p < 0.05) in the tocilizumab group. In contrast, tocilizumab had only modest or no effects on the other examined cytokines. CONCLUSIONS:Tocilizumab led to a selective and substantial increase in IP-10 and MIP-1β during the acute phase of NSTEMI, with no or only minor effects on the other measured cytokines. ClinicalTrials.gov, NCT01491074.
RCT Entities:
AIM: To evaluate the effect of interleukin-6 inhibition with tocilizumab on the cytokine network in patients with acute non-ST-elevation myocardial infarction (NSTEMI). METHODS: 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 points in time during hospitalisation, and at follow-up after 3 and 6 months. Cytokines (n = 27) were analysed with a multiplex cytokine assay. RESULTS: Using a mixed between-within subjects analysis of variance, we observed a significant (p < 0.001) between-group difference in changes for interferon gamma-inducible protein (IP-10) and macrophage inflammatory protein-1β (MIP-1β), due to significant increases in the tocilizumab group during hospitalisation (i.e., IP-10 median change from baseline during hospitalisation (mΔ), placebo: 3 (-60, 68) pg/ml vs tocilizumab: 209 (69, 335) pg/ml; MIP-1β mΔ, placebo: 5 (-2, 12) pg/ml vs tocilizumab: 39 (24, 63) pg/ml). MIP-1β was inversely correlated to troponin T (r = -0.28, p < 0.05) and neutrophils (r = -0.32, p < 0.05) in the tocilizumab group. In contrast, tocilizumab had only modest or no effects on the other examined cytokines. CONCLUSIONS:Tocilizumab led to a selective and substantial increase in IP-10 and MIP-1β during the acute phase of NSTEMI, with no or only minor effects on the other measured cytokines. ClinicalTrials.gov, NCT01491074.
Authors: Aly M Abdelrahman; Yousuf Al Suleimani; Asem Shalaby; Mohammed Ashique; Priyadarsini Manoj; Badreldin H Ali Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2019-04-25 Impact factor: 3.000
Authors: Marc Jonathan George; Nur Hayati Jasmin; Valerie Taylor Cummings; Angela Richard-Loendt; Francesca Launchbury; Kevin Woollard; Tabitha Turner-Stokes; Ana Isabel Garcia Diaz; Mark Lythgoe; Daniel James Stuckey; Aroon Dinesh Hingorani; Derek William Gilroy Journal: JACC Basic Transl Sci Date: 2021-04-07
Authors: Marc J George; Ola Kleveland; Jorge Garcia-Hernandez; Jutta Palmen; Ruth Lovering; Rune Wiseth; Pål Aukrust; Jorgen Engmann; Jan Kristian Damås; Aroon D Hingorani; Lars Gullestad; Juan P Casas; Thor Ueland Journal: J Am Heart Assoc Date: 2020-06-09 Impact factor: 5.501
Authors: Martin A S Meyer; Sebastian Wiberg; Johannes Grand; Jesper Kjaergaard; Christian Hassager Journal: Trials Date: 2020-10-20 Impact factor: 2.279