In:
Critical Care, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2015-12)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1364-8535
DOI:
10.1186/s13054-015-1129-9
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2015
detail.hit.zdb_id:
2051256-9
