Combined inhibition of complement and CD14 improved outcome in porcine polymicrobial sepsis.

Autor: Skjeflo EW; Research Laboratory, Nordland Hospital, Prinsens Gate 164, 8092, Bodø, Norway. espenwskjeflo@gmail.com.; Faculty of Health Sciences, K. G. Jebsen TREC, University of Tromsø, 9037, Tromsø, Norway. espenwskjeflo@gmail.com., Sagatun C; Department of Surgery, Nordland Hospital, Prinsens Gate 164, 8092, Bodø, Norway. c.sagatun@gmail.com., Dybwik K; Department of Anestesiology, Nordland Hospital, Prinsens Gate 164, 8092, Bodø, Norway. kdybwik@gmail.com.; Faculty of Professional Studies, University of Nordland, Universitetsaleen 11, 8049, Bodø, Norway. kdybwik@gmail.com., Aam S; Faculty of Medicine, Ludwig Maximillian University, Professor Huber Platz 2, 80539, Munich, Germany. sturla.aam@gmail.com., Urving SH; Department of Anestesiology, Nordland Hospital, Prinsens Gate 164, 8092, Bodø, Norway. shurving@gmail.com., Nunn MA; Volution Immuno Pharmaceuticals Limited, 5 Argosy Court, Whitley Business Park, Coventry, CV3 4GA, UK. miles.nunn@gmail.com., Fure H; Research Laboratory, Nordland Hospital, Prinsens Gate 164, 8092, Bodø, Norway. Hilde.Fure@nlsh.no., Lau C; Research Laboratory, Nordland Hospital, Prinsens Gate 164, 8092, Bodø, Norway. Corinna.Lau@nlsh.no., Brekke OL; Research Laboratory, Nordland Hospital, Prinsens Gate 164, 8092, Bodø, Norway. Ole.Lars.Brekke@nlsh.no.; Faculty of Health Sciences, K. G. Jebsen TREC, University of Tromsø, 9037, Tromsø, Norway. Ole.Lars.Brekke@nlsh.no., Huber-Lang M; Department of Traumatology, Center of Surgery, University of Ulm, Albert Einstein Allee 23, 89081, Ulm, Germany. Markus.Huber-Lang@uniklinik-ulm.de., Espevik T; Centre of Molecular Inflammation Research, and Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Høgskoleringen 1, 7491, Trondheim, Norway. terje.espevik@ntnu.no., Barratt-Due A; Department of Immunology, Oslo University Hospital and K.G. Jebsen IRC, University of Oslo, PB 4960 Nydalen, 0424, Oslo, Norway. andreas.barrattdue@gmail.com.; Division of Emergencies and Critical Care, Rikshospitalet, Oslo University Hospital Oslo, Sognsvannsveien 20, 0372, Oslo, Norway. andreas.barrattdue@gmail.com., Nielsen EW; Faculty of Health Sciences, K. G. Jebsen TREC, University of Tromsø, 9037, Tromsø, Norway. erik.waage.nielsen@gmail.com.; Department of Anestesiology, Nordland Hospital, Prinsens Gate 164, 8092, Bodø, Norway. erik.waage.nielsen@gmail.com.; Faculty of Professional Studies, University of Nordland, Universitetsaleen 11, 8049, Bodø, Norway. erik.waage.nielsen@gmail.com.; Department of Immunology, Oslo University Hospital and K.G. Jebsen IRC, University of Oslo, PB 4960 Nydalen, 0424, Oslo, Norway. erik.waage.nielsen@gmail.com., Mollnes TE; Research Laboratory, Nordland Hospital, Prinsens Gate 164, 8092, Bodø, Norway. t.e.mollnes@medisin.uio.no.; Faculty of Health Sciences, K. G. Jebsen TREC, University of Tromsø, 9037, Tromsø, Norway. t.e.mollnes@medisin.uio.no.; Centre of Molecular Inflammation Research, and Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Høgskoleringen 1, 7491, Trondheim, Norway. t.e.mollnes@medisin.uio.no.; Department of Immunology, Oslo University Hospital and K.G. Jebsen IRC, University of Oslo, PB 4960 Nydalen, 0424, Oslo, Norway. t.e.mollnes@medisin.uio.no.
Jazyk: angličtina
Zdroj: Critical care (London, England) [Crit Care] 2015 Nov 27; Vol. 19, pp. 415. Date of Electronic Publication: 2015 Nov 27.
DOI: 10.1186/s13054-015-1129-9
Abstrakt: Introduction: Sepsis is an exaggerated and dysfunctional immune response to infection. Activation of innate immunity recognition systems including complement and the Toll-like receptor family initiate this disproportionate inflammatory response. The aim of this study was to explore the effect of combined inhibition of the complement component C5 and the Toll-like receptor co-factor CD14 on survival, hemodynamic parameters and systemic inflammation including complement activation in a clinically relevant porcine model of polymicrobial sepsis.
Methods: Norwegian landrace piglets (4 ± 0.5 kg) were blindly randomized to a treatment group (n = 12) receiving the C5 inhibitor coversin (OmCI) and anti-CD14 or to a positive control group (n = 12) receiving saline. Under anesthesia, sepsis was induced by a 2 cm cecal incision and the piglets were monitored in standard intensive care for 8 hours. Three sham piglets had a laparotomy without cecal incision or treatment. Complement activation was measured as sC5b-9 using enzyme immunoassay. Cytokines were measured with multiplex technology.
Results: Combined C5 and CD14 inhibition significantly improved survival (p = 0.03). Nine piglets survived in the treatment group and four in the control group. The treatment group had significantly lower pulmonary artery pressure (p = 0.04) and ratio of pulmonary artery pressure to systemic artery pressure (p < 0.001). Plasma sC5b-9 levels were significantly lower in the treatment group (p < 0.001) and correlated significantly with mortality (p = 0.006). IL-8 and IL-10 were significantly (p < 0.05) lower in the treatment group.
Conclusions: Combined inhibition of C5 and CD14 significantly improved survival, hemodynamic parameters and inflammation in a blinded, randomized trial of porcine polymicrobial sepsis.
Databáze: MEDLINE
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