Combined inhibition of complement and CD14 improved outcome in porcine polymicrobial sepsis
AuthorSkjeflo, Espen Waage; Sagatun, Caroline; Dybwik, Knut; Aam, Sturla; Urving, Sven Haakon; Nunn, Miles A.; Fure, Hilde; Lau, Corinna; Brekke, Ole Lars; Huber-Lang, Markus; Barratt-Due, Andreas; Nielsen, Erik Waage; Mollnes, Tom Eirik
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.