• Alginate microbeads are complement compatible, in contrast to polycation containing microcapsules, as revealed in a human whole blood model 

      Rokstad, Anne Mari; Brekke, Ole Lars; Steinkjer, Bjørg; Ryan, Liv; Kolláriková, Gabriela; Strand, Berit Løkensgard; Skjåk-Bræk, Gudmund; Lacík, Igor; Espevik, Terje; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)
      Alginate microbeads and microcapsules are presently under evaluation for future cell-based therapy. Defining their inflammatory properties with regard to humans is therefore essential. A lepirudine-based human whole blood model was used as an inflammation predictor by measuring complement and leukocyte stimulation. Alginate microbeads were complement-compatible since they did not activate complement ...
    • Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation 

      Ørning, Mathias Pontus; Hoem, Kine Samseth; Coron, Abba Elizabeth; Skjåk-Bræk, Gudmund; Mollnes, Tom Eirik; Brekke, Ole Lars; Espevik, Terje; Rokstad, Anne Mari (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-03-16)
      The inflammatory potential of 12 types of alginate-based microspheres was assessed in a human whole blood model. The inflammatory potential could be categorized from low to high based on the four main alginate microsphere types; alginate microbeads, liquefied core poly-l-ornithine (PLO)-containing microcapsules, liquefied core poly-l-lysine (PLL)-containing microcapsules, and solid core PLL-containing ...
    • CD14 and complement crosstalk and largely mediate the transcriptional response to Escherichia coli in human whole blood as revealed by DNA microarray 

      Lau, Corinna; Nygård, Ståle; Fure, Hilde; Olstad, Ole Kristoffer; Holden, Marit; Lappegård, Knut Tore; Brekke, Ole Lars; Espevik, Terje; Hovig, Johannes Eivind; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-02-23)
      Systemic inflammation like in sepsis is still lacking specific diagnostic markers and effective therapeutics. The first line of defense against intruding pathogens and endogenous damage signals is pattern recognition by e.g., complement and Toll-like receptors (TLR). Combined inhibition of a key complement component (C3 and C5) and TLR-co-receptor CD14 has been shown to attenuate certain systemic ...
    • Cholesterol crystal-induced endothelial cell activation is complement-dependent and mediated by TNF 

      Nymo, Stig Haugset; Niyonzima, Nathalie; Espevik, Terje; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel, 2014-07-05)
      Cholesterol crystals are known to be a hallmark of atherosclerosis with recent studies demonstrating deposition of these crystals in early fatty streak formation as well as penetrating the intima following plaque rupture. Inflammation has also become a central focus in atheroma development and endothelial cell activation is recognized as necessary for the recruitment of inflammatory cells to the ...
    • Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome 

      Thomas, Anub Mathew; Schjalm, Camilla; Nilsson, Per; Lindenskov, Paal Helge H.; Rørtveit, Runa; Solberg, Rønnaug; Saugstad, Ola Didrik; Berglund, Magnus M.; Strömberg, Patrik; Lau, Corinna; Espevik, Terje; Jansen, Johan Høgset; Castellheim, Albert; Mollnes, Tom Eirik; Barratt-Due, Andreas (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-02-27)
      <p><i>Background</i>: Meconium aspiration syndrome (MAS) is a severe lung condition affecting newborns and it can lead to a systemic inflammatory response. We previously documented complement activation and cytokine release in a piglet MAS model. Additionally, we showed ex vivo that meconium-induced inflammation was dependent on complement and Toll-like receptors.</p> <p><i>Objectives</i>: To ...
    • Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis 

      Hellerud, Bernt C; Orrem, Hilde L.; Dybwik, Knut Gustav; Pischke, Søren Erik; Barratt-Due, Andreas; Castellheim, Albert; Fure, Hilde; Bergseth, Grete; Christiansen, Dorte; Nunn, Miles A.; Espevik, Terje; Lau, Corinna; Brandtzæg, Petter; Nielsen, Erik Waage; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-02-27)
      Background<br> Fulminant meningococcal sepsis, characterized by overwhelming innate immune activation, mostly affects young people and causes high mortality. This study aimed to investigate the effect of targeting two key molecules of innate immunity, complement component C5, and co-receptor CD14 in the Toll-like receptor system, on the inflammatory response in meningococcal sepsis.<p> Methods ...
    • Combined inhibition of complement and CD14 attenuates bacteria-induced inflammation in human whole blood more efficiently than antagonizing the toll-like receptor 4-MD2 complex 

      Gustavsen, Alice; Nymo, Stig Haugset; Landsem, Anne; Christiansen, Dorte; Ryan, Liv; Husebye, Harald; Lau, Corinna; Pischke, Søren Erik; Lambris, John D.; Espevik, Terje; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-03-14)
      <i>Background</i>: Single inhibition of the Toll-like receptor 4 (TLR4)–MD2 complex failed in treatment of sepsis. CD14 is a coreceptor for several TLRs, including TLR4 and TLR2. The aim of this study was to investigate the effect of single TLR4-MD2 inhibition by using eritoran, compared with the effect of CD14 inhibition alone and combined with the C3 complement inhibitor compstatin (Cp40), on the ...
    • Complement component 5 does not interfere with physiological hemostasis but is essential for Escherichia coli-induced coagulation accompanied by Toll-like receptor 4 

      Landsem, Anne; Fure, Hilde; Ludviksen, Judith K; Christiansen, Dorte; Lau, Corinna; Mathisen, Monica Dammen; Bergseth, Grete; Nymo, Stig Haugset; Lappegård, Knut Tore; Woodruff, T. M.; Espevik, Terje; Mollnes, Tom Eirik; Brekke, Ole-Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-12-19)
      There is a close cross‐talk between complement, Toll‐like receptors (TLRs) and coagulation. The role of the central complement component 5 (C5) in physiological and pathophysiological hemostasis has not, however, been fully elucidated. This study examined the effects of C5 in normal hemostasis and in <i>Escherichia coli</i>‐induced coagulation and tissue factor (TF) up‐regulation. Fresh whole blood ...
    • The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis 

      Hovland, Anders; Jonasson, Lena; Garred, Peter; Yndestad, Arne; Aukrust, Pål; Lappegård, Knut Tore; Espevik, Terje; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-06-05)
      Despite recent medical advances, atherosclerosis is a global burden accounting for numerous deaths and hospital admissions. Immune-mediated inflammation is a major component of the atherosclerotic process, but earlier research focus on adaptive immunity has gradually switched towards the role of innate immunity. The complement system and toll-like receptors (TLRs), and the crosstalk between them, ...
    • Dual inhibition of complement and Toll-like receptors as a novel approach to treat inflammatory diseases-C3 or C5 emerge together with CD14 as promising targets. 

      Barratt-Due, Andreas; Pischke, Søren Erik; Nilsson, Per; Espevik, Terje; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-08-31)
      The host is protected by pattern recognition systems, including complement and TLRs, which are closely cross-talking. If improperly activated, these systems might induce tissue damage and disease. Inhibition of single downstream proinflammatory cytokines, such as TNF, IL-1β, and IL-6, have failed in clinical sepsis trials, which might not be unexpected, given the substantial amounts of mediators ...
    • Gene expression profiling of Gram-negative bacteria-induced inflammation in human whole blood: The role of complement and CD14-mediated innate immune response 

      Lau, Corinna; Olstad, Ole Kristoffer; Holden, Marit; Nygård, Ståle; Fure, Hilde; Lappegård, Knut Tore; Brekke, Ole Lars; Espevik, Terje; Hovig, Johannes Eivind; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-05-30)
      Non-sterile pathogen-induced sepsis and sterile inflammation like in trauma or ischemia–reperfusion injury may both coincide with the life threatening systemic inflammatory response syndrome and multi-organ failure. Consequently, there is an urgent need for specific biomarkers in order to distinguish sepsis from sterile conditions. The overall aim of this study was to uncover putative sepsis ...
    • 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 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 ...
    • Phagocytosis of live and dead Escherichia coli and Staphylococcus aureus in human whole blood is markedly reduced by combined inhibition of C5aR1 and CD14 

      Skjeflo, Espen Waage; Christiansen, Dorte; Landsem, Anne; Stenvik, Jørgen; Woodruff, T. M.; Espevik, Terje; Nielsen, Erik Waage; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-05-15)
      <i>Background</i> - Sepsis is a dysregulated host response to infection. The aim of this study was to investigate the effects of complement- and CD14 inhibition on phagocytosis of live and dead Gram-negative and Gram-positive bacteria in human whole blood.<p> <p><i>Methods</i> - Lepirudin-anticoagulated blood was incubated with live or dead <i>E. coli</i> or <i>S. aureus</i> at 37 °C for 120 min ...
    • Staphylococcus aureus-induced complement activation promotes tissue factor-mediated coagulation 

      Skjeflo, Espen Waage; Christiansen, Dorte; Fure, Hilde; Ludviksen, Judith K; Woodruff, Trent M.; Espevik, Terje; Nielsen, Erik Waage; Brekke, Ole-Lars; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-02-13)
      <p><i>Background - </i>There is extensive cross‐talk between the complement system, the Toll‐like receptors (TLRs), and hemostasis. Consumptive coagulopathy is a hallmark of sepsis, and is often mediated through increased tissue factor (TF) expression. <p><i>Objectives - </i>To study the relative roles of complement, TLRs and TF in <i>Staphylococcus aureus</i>‐induced coagulation. <p><i>Methods - ...