Organ inflammation in porcine Escherichia coli sepsis is markedly attenuated by combined inhibition of C5 and CD14.

Egge, Kjetil H; Thorgersen, Ebbe B; Pischke, Søren E; Lindstad, Julie K; Pharo, Anne; Bongoni, Anjan; Rieben, Robert; Nunn, Miles A; Barratt-Due, Andreas; Mollnes, Tom E (2015). Organ inflammation in porcine Escherichia coli sepsis is markedly attenuated by combined inhibition of C5 and CD14. Immunobiology, 220(8), pp. 999-1005. Elsevier 10.1016/j.imbio.2015.04.002

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Sepsis is an infection-induced systemic inflammatory syndrome, potentially causing organ failure. We previously showed attenuating effects on inflammation, thrombogenicity and haemodynamics by inhibiting the Toll-like receptor co-factor CD14 and complement factor C5 in a porcine Escherichia coli-induced sepsis model. The present study explored the effect on organ inflammation in these pigs. Tissue samples were examined from the combined treatment group (n = 8), the positive (n = 8) and negative (n = 6) control groups after 4h of sepsis. Inflammatory biomarkers were measured using ELISA, multiplex and qPCR analysis. Combined inhibition of C5 and CD14 markedly attenuated IL-1β by 31-66% (P < 0.05) and IL-6 by 54-96% (P < 0.01) in liver, kidney, lung and spleen; IL-8 by 65-100% in kidney, lung, spleen, and heart (P < 0.05) and MCP-1 by 46-69% in liver, kidney, spleen and heart (P < 0.05). Combined inhibition significantly attenuated tissue factor mRNA upregulation in spleen (P < 0.05) and IP-10 mRNA upregulation in four out of five organs. Finally, C5aR mRNA downregulation was prevented in heart and kidney (P < 0.05). Combined inhibition of C5 and CD14 thus markedly attenuated inflammatory responses in all organs examined. The anti-inflammatory effects observed in lung and heart may explain the delayed haemodynamic disturbances observed in septic pigs receiving combined inhibition of C5 and CD14.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Herz und Gefässe

UniBE Contributor:

Bongoni, Anjan and Rieben, Robert

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0171-2985

Publisher:

Elsevier

Language:

English

Submitter:

Verena de Serra Frazao-Bill

Date Deposited:

13 Apr 2016 12:58

Last Modified:

20 Feb 2019 09:37

Publisher DOI:

10.1016/j.imbio.2015.04.002

PubMed ID:

25956456

Uncontrolled Keywords:

CD14, Complement, Inflammation, Porcine, Sepsis, Tissue

BORIS DOI:

10.7892/boris.80584

URI:

https://boris.unibe.ch/id/eprint/80584

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