• Complement activation is associated with poor outcome after out-of-hospital cardiac arrest 

      Chaban, Viktoriia; Nakstad, Espen R.; Stær-Jensen, Henrik; Schjalm, Camilla; Seljeflot, Ingebjørg; Vaage, Ingvar Jarle; Lundqvist, Christofer; Saltyte Benth, Jurate; Sunde, Kjetil; Mollnes, Tom Eirik; Andersen, Geir Øystein; Pischke, Soeren (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-06-11)
      Background - Cardiopulmonary resuscitation after cardiac arrest initiates a whole-body ischemia-reperfusion injury, which may activate the innate immune system, including the complement system. We hypothesized that complement activation and subsequent release of soluble endothelial activation markers were associated with cerebral outcome including death.<p> <p>Methods - Outcome was assessed at ...
    • Complement Is Activated During Normothermic Machine Perfusion of Porcine and Human Discarded Kidneys 

      Jager, Neeltina M.; Venema, Leonie H.; Arykbaeva, Asel S.; Meter-Arkema, Anita H.; Ottens, Petra J.; van Kooten, Cees; Mollnes, Tom Eirik; Alwayn, Ian P. J.; Leuvenink, Henri G. D.; Pischke, Soeren (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-07-13)
      Background: The gap between demand and supply of kidneys for transplantation necessitates the use of kidneys from extended criteria donors. Transplantation of these donor kidneys is associated with inferior results, reflected by an increased risk of delayed graft function. Inferior results might be explained by the higher immunogenicity of extended criteria donor kidneys. Normothermic machine ...
    • A conformational change of complement C5 is required for thrombin-mediated cleavage, revealed by a novel ex vivo human whole blood model preserving full thrombin activity 

      Nilsson, Per; Johnson, Christina; Quach, Huy Quang; Macpherson, Alex; Durrant, Oliver; Pischke, Soeren; Fure, Hilde; Landsem, Anne; Bergseth, Grete; Schjalm, Camilla; Haugaard-Kedström, Linda M.; Huber-Lang, Markus; van den Elsen, Jean; Brekke, Ole-Lars; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-09-15)
      Thrombin activation of C5 connects thrombosis to inflammation. Complement research in whole blood ex vivo necessitates anticoagulation, which potentially interferes with the inflammatory modulation by thrombin. We challenged the concept of thrombin as an activator of native C5 by analyzing complement activation and C5 cleavage in human whole blood anticoagulated with Gly-Pro-Arg-Pro (GPRP), a peptide ...
    • Elevated plasma sTIM-3 levels in patients with severe COVID-19 

      Ueland, Thor; Heggelund, Lars; Lind, Andreas; Holten, Aleksander Rygh; Tonby, Kristian; Michelsen, Annika; Jenum, Synne; Jørgensen, Marthe Jøntvedt; Barratt-Due, Andreas; Skeie, Linda Gail; Nordøy, Ingvild; Aanensen Fraz, Mai Sasaki; Paulsen, Else Quist; Pischke, Soeren; Johal, Simreen Kaur; Hesstvedt, Liv; Bogen, Mette; Fevang, Børre; Halvorsen, Bente; Müller, Fredrik; Bekken, Gry Kloumann; Mollnes, Tom Eirik; Dudman, Susanne Gjeruldsen; Aukrust, Pål; Dyrhol-Riise, Anne Ma; Holter, Jan Cato (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-09-21)
      <i>Background</i> - The pathogenesis of coronavirus disease 2019 (COVID-19) is still incompletely understood, but it seems to involve immune activation and immune dysregulation.<p> <p><i>Objective</i> - We examined the parameters of activation of different leukocyte subsets in COVID-19–infected patients in relation to disease severity.<p> <p><i>Methods</i> - We analyzed plasma levels of ...
    • Endotoxin removal in septic shock with the Alteco LPS Adsorber was safe but showed no benefit compared to placebo in the double-blind randomized controlled trial - the Asset Study 

      Lipcsey, Miklos; Tenhunen, Jyrki; Pischke, Soeren; Kuitunen, Anne; Flaatten, Hans; De Geer, Lina; Sjölin, Jan; Frithiof, Robert; Chew, Michelle S.; Bendel, Stepani; Kawati, Rafael; Larsson, Anders; Mollnes, Tom Eirik; Tønnessen, Tor Inge; Rubertsson, Sten (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-08)
      <i>Purpose</i>: Lipopolysaccharides (LPS) are presumed to contribute to the inflammatory response in sepsis. We investigated if extracorporeal Alteco LPS Adsorber for LPS removal in early gram-negative septic shock was feasible and safe. Also, effects on endotoxin level, inflammatory response, and organ function were assessed.<br><br> <i>Methods</i>: A pilot, double-blinded, randomized, Phase ...
    • Increased interleukin-6 and macrophage chemoattractant protein-1 are associated with respiratory failure in COVID-19 

      Jørgensen, Marthe Jøntvedt; Holter, Jan Cato; Christensen, Erik; Schjalm, Camilla; Tonby, Kristian; Pischke, Soeren; Jenum, Synne; Skeie, Linda Gail; Nur, Sarah; Lind, Andreas; Opsand, Hanne; Enersen, Tone Burvald; Grøndahl, Ragnhild; Hermann, Anne; Dudman, Susanne Gjeruldsen; Müller, Fredrik; Ueland, Thor; Mollnes, Tom Eirik; Aukrust, Pål; Heggelund, Lars; Holten, Aleksander Rygh; Dyrhol-Riise, Anne Ma (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-12-10)
      In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment. In this study we analyzed plasma cytokines in COVID-19 patients and investigated their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Hospitalized patients (n = 34) with confirmed COVID-19 were recruited into a ...
    • Intracellular Complement Component 3 Attenuated Ischemia-Reperfusion Injury in the Isolated Buffer-Perfused Mouse Heart and Is Associated With Improved Metabolic Homeostasis 

      Torp, May-Kristin; Ranheim, Trine; Schjalm, Camilla; Hjorth, Marit; Heiestad, Christina Mathisen; Dalen, Knut Tomas; Nilsson, Per; Mollnes, Tom Eirik; Pischke, Soeren; Lien, Egil; Vaage, Ingvar Jarle; Yndestad, Arne; Stensløkken, Kåre-Olav (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-04-01)
      The innate immune system is rapidly activated during myocardial infarction and blockade of extracellular complement system reduces infarct size. Intracellular complement, however, appears to be closely linked to metabolic pathways and its role in ischemia-reperfusion injury is unknown and may be different from complement activation in the circulation. The purpose of the present study was to investigate ...
    • Synthetic Oligodeoxynucleotide CpG Motifs Activate Human Complement through Their Backbone Structure and Induce Complement-Dependent Cytokine Release 

      de Boer, Eline; Sokolova, Marina; Quach, Huy Quang; Mc Adam, Karin Ekholt; Götz, Maximilian P.; Chaban, Viktoriia; Vaage, Ingvar Jarle; Fageräng, Beatrice Linnea Christina; Woodruff, Trent M.; Garred, Peter; Nilsson, Per; Mollnes, Tom Eirik; Pischke, Soeren (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-11-01)
      Bacterial and mitochondrial DNA, sharing an evolutionary origin, act as danger-associated molecular patterns in infectious and sterile inflammation. They both contain immunomodulatory CpG motifs. Interactions between CpG motifs and the complement system are sparsely described, and mechanisms of complement activation by CpG remain unclear. Lepirudin-anticoagulated human whole blood and plasma were ...
    • Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients 

      Holter, Jan Cato; Pischke, Soeren; de Boer, Eline; Lind, Andreas; Jenum, Synne; Holten, Aleksander Rygh; Tonby, Kristian; Barratt-Due, Andreas; Sokolova, Marina; Schjalm, Camilla; Chaban, Viktoriia; Kolderup, Anette; Tran, Trung; Tollefsrud Gjølberg, Torleif; Skeie, Linda Gail; Hesstvedt, Liv; Ormåsen, Vidar; Fevang, Børre; Austad, Cathrine; Muller, Karl Erik; Fladeby, Cathrine; Holberg-Petersen, Mona; Halvorsen, Bente; Müller, Fredrik; Aukrust, Pål; Dudman, Susanne Gjeruldsen; Ueland, Thor; Andersen, Jan Terje; Lund-Johansen, Fridtjof; Heggelund, Lars; Dyrhol-Riise, Anne Ma; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-09-17)
      The new SARS-CoV-2 pandemic leads to COVID-19 with respiratory failure, substantial morbidity, and significant mortality. Overactivation of the innate immune response is postulated to trigger this detrimental process. The complement system is a key player in innate immunity. Despite a few reports of local complement activation, there is a lack of evidence that the degree of systemic complement ...
    • Systemic inflammation early after kidney transplantation is associated with long-term graft loss: a cohort study 

      Heldal, Torbjørn Fossum; Åsberg, Anders; Ueland, Thor; Reisæter, Anna Varberg; Pischke, Soeren; Mollnes, Tom Eirik; Aukrust, Pål; Reinholt, Finn P.; Hartmann, Anders; Heldal, Kristian; Jenssen, Trond (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-10-02)
      Background: Early graft loss following kidney transplantation is mainly a result of acute rejection or surgical complications, while long-term kidney allograft loss is more complex. We examined the association between systemic inflammation early after kidney transplantation and long-term graft loss, as well as correlations between systemic inflammation scores and inflammatory findings in biopsies 6 ...
    • Systemic inflammation persists the first year after mild traumatic brain injury: Results from the Prospective Trondheim Mild Traumatic Brain Injury Study 

      Chaban, Viktoriia; Clarke, Gerard; Skandsen, Toril; Islam, Rakibul; Einarsen, Cathrine Elisabeth; Vik, Anne; Damås, Jan Kristian; Mollnes, Tom Eirik; Håberg, Asta; Pischke, Soeren (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-06-03)
      Innate immune activation has been attributed a key role in traumatic brain injury (TBI) and successive morbidity. In mild TBI (mTBI), however, the extent and persistence of innate immune activation are unknown. We determined plasma cytokine level changes over 12 months after an mTBI in hospitalized and non-hospitalized patients compared with community controls; and examined their associations to ...
    • Thrombin Differentially Modulates the Acute Inflammatory Response to Escherichia coli and Staphylococcus aureus in Human Whole Blood 

      Johnson, Christina; Quach, Huy Quang; Lau, Corinna; Ekholt, Karin; Espevik, Terje; Woodruff, Trent M.; Pischke, Soeren; Mollnes, Tom Eirik; Nilsson, Per (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-06-15)
      Thrombin plays a central role in thromboinflammatory responses, but its activity is blocked in the common ex vivo human whole blood models, making an ex vivo study of thrombin effects on thromboinflammatory responses unfeasible. In this study, we exploited the anticoagulant peptide Gly-Pro-Arg-Pro (GPRP) that blocks fibrin polymerization to study the effects of thrombin on acute inflammation in ...