Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
PROTECTIVE EFFECTS OF THE COMPLEMENT INHIBITOR COMPSTATIN CP40 IN HEMORRHAGIC SHOCK
Tech Univ Munich, Klinikum Rechts Isar, Dept Trauma Surg, Expt Trauma Surg, Munich, Germany.ORCID iD: 0000-0001-5104-9881
Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA;Univ Basel, Dept Pharmaceut Sci, Basel, Switzerland.
Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany.
Univ Ulm, Inst Clin & Expt Trauma Immunol, Helmholtzstr 8-2, D-89081 Ulm, Germany.
Show others and affiliations
2019 (English)In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 51, no 1, p. 78-87Article in journal (Refereed) Published
Abstract [en]

Trauma-induced hemorrhagic shock (HS) plays a decisive role in the development of immune, coagulation, and organ dysfunction often resulting in a poor clinical outcome. Imbalanced complement activation is intricately associated with the molecular danger response and organ damage after HS. Thus, inhibition of the central complement component C3 as turnstile of both inflammation and coagulation is hypothesized as a rational strategy to improve the clinical course afterHS. Applying intensive care conditions, anaesthetized, monitored, and protectively ventilated nonhuman primates (NHP; cynomolgusmonkeys) received a pressure-controlled severe HS (60min at mean arterial pressure 30 mmHg) with subsequent volume resuscitation. Thirty minutes after HS, animals were randomly treated with either an analog of the C3 inhibitor compstatin (i.e., Cp40) in saline (n =4) or with saline alone (n =4). The observation period lasted 300 min after induction of HS. We observed improved kidney function in compstatin Cp40-treated animals after HS as determined by improved urine output, reduced damage markers and a tendency of less histopathological signs of acute kidney injury. Sham-treated animals revealed classical signs ofmucosal edema, especially in the ileum and colon reflected by worsened microscopic intestinal injury scores. In contrast, Cp40-treated HS animals exhibited only minor signs of organ edema and significantly less intestinal damage. Furthermore, early systemic inflammation and coagulation dysfunction were both ameliorated by Cp40. The data suggest that therapeutic inhibition of C3 is capable to significantly improve immune, coagulation, and organ function and to preserve organ-barrier integrity early after traumatic HS. C3-targeted complement inhibition may therefore reflect a promising therapeutic strategy in fighting fatal consequences of HS.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS , 2019. Vol. 51, no 1, p. 78-87
Keywords [en]
Complement, hemorrhagic shock, inflammation, intestine, kidney, nonhuman primate
National Category
Immunology
Identifiers
URN: urn:nbn:se:uu:diva-381929DOI: 10.1097/SHK.0000000000001127ISI: 000462687800010PubMedID: 29461464OAI: oai:DiVA.org:uu-381929DiVA, id: diva2:1305697
Funder
EU, FP7, Seventh Framework ProgrammeAvailable from: 2019-04-18 Created: 2019-04-18 Last updated: 2019-04-18Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records

Nilsson, KristinaNilsson, Bo

Search in DiVA

By author/editor
van Griensven, MartijnBraun, Christian K.Primikyri, AlexandraNilsson, KristinaNilsson, Bo
By organisation
Experimental and Clinical OncologyClinical Immunology
In the same journal
Shock
Immunology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 33 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf