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Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation
(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 ...
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
(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 ...
Effect of the anticoagulant, storage time and temperature of blood samples on the concentrations of 27 multiplex assayed cytokines – Consequences for defining reference values in healthy humans
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-06-06)
Cytokines are potentially useful biomarkers of sepsis and other inflammatory conditions. Many cytokines can be released by leukocytes and platelets after sampling. The sampling and processing techniques are consequently critically important to measure the <i>in vivo</i> levels. We therefore examined the effects of four different anticoagulants, EDTA, citrate, lepirudin, heparin compared to serum, ...
Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes
(Journal article; Manuskript; Tidsskriftartikkel; Peer reviewed; Preprint, 2017-04-10)
Intravenously injected nanopharmaceuticals, including PEGylated nanoparticles, induce adverse cardiopulmonary reactions in sensitive human subjects, and these reactions are highly reproducible in pigs. Although the underlying mechanisms are poorly understood, roles for both the complement system and reactive macrophages have been implicated. Here, we show the dominance and importance of robust ...
Alginate microbeads are complement compatible, in contrast to polycation containing microcapsules, as revealed in a human whole blood model
(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 ...
Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn
(Journal article; Tidsskriftartikkel; Peer reviewed, 2015-11-13)
Eculizumab is a humanized IgG2/4 chimeric anti-complement C5 antibody used to treat patients with
paroxysmal nocturnal hemoglobinuria (PNH) or atypical hemolytic uremic syndrome. The aim of this
study was to evaluate whether or not the complement activity in newborns from pregnant women who
receive eculizumab is impaired. A novel eculizumab-C5 complex (E-C5) specific assay was developed
and ...
Ficolins do not alter host immune responses to lipopolysaccharide-induced inflammation in vivo
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-06-20)
Ficolins are a family of pattern recognition molecules that are capable of activating the lectin pathway of complement. A limited number of reports have demonstrated a protective role of ficolins in animal models of infection. In addition, an immune modulatory role of ficolins has been suggested. Yet, the contribution of ficolins to inflammatory disease processes remains elusive. To address this, ...
Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-03-03)
Inhibition of complement factor 5 (C5) reduced myocardial infarction in animal studies, while
no benefit was found in clinical studies. Due to lack of cross-reactivity of clinically used C5 antibodies, different inhibitors were used in animal and clinical studies. Coversin (Ornithodoros moubata complement inhibitor, OmCI) blocks C5 cleavage and binds leukotriene B4 in humans and pigs. We hypothesized ...
Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis
(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 ...
IL-6 receptor inhibition by tocilizumab attenuated expression of C5a receptor 1 and 2 in non-ST-elevation myocardial infarction
(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 ...