Evidence map›Paper›PMID 29486477›Full record

ArticleNeonatology2018

Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome.

Anub Mathew Thomas, Camilla Schjalm, Per H Nilsson, Paal H H Lindenskov, Runa Rørtveit, Rønnaug Solberg, Ola Didrik Saugstad, Magnus M Berglund, Patrik Strömberg, Corinna Lau and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Neonatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 2 countries.

Anub Mathew ThomasDepartment of Immunology, Oslo University Hospital and K.G. Jebsen IRC, University of Oslo, Oslo, Norway.
Camilla SchjalmDepartment of Immunology, Oslo University Hospital and K.G. Jebsen IRC, University of Oslo, Oslo, Norway.
Per H NilssonDepartment of Immunology, Oslo University Hospital and K.G. Jebsen IRC, University of Oslo, Oslo, Norway.
Paal H H LindenskovDivision of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway.
Runa RørtveitFaculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo/Ås, Norway.
Rønnaug SolbergDepartment of Pediatric Research, Oslo University Hospital, University of Oslo, Oslo, Norway.
Ola Didrik SaugstadDepartment of Pediatric Research, Oslo University Hospital, University of Oslo, Oslo, Norway.
Magnus M BerglundResearch and Translational Science, Swedish Orphan Biovitrum, Stockholm, Sweden.
Patrik StrömbergResearch and Translational Science, Swedish Orphan Biovitrum, Stockholm, Sweden.
Corinna LauResearch Laboratory, Nordland Hospital, Bodø, Norway.
Terje EspevikCenter of Molecular Inflammatory Research and Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Johan Høgset JansenFaculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo/Ås, Norway.
Albert CastellheimDepartment of Anaesthesiology and Intensive Care, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Tom Eirik MollnesDepartment of Immunology, Oslo University Hospital and K.G. Jebsen IRC, University of Oslo, Oslo, Norway.
Andreas Barratt-DueDepartment of Immunology, Oslo University Hospital and K.G. Jebsen IRC, University of Oslo, Oslo, Norway.
Oslo University Hospital · NONorwegian University of Life Sciences · NOSwedish Orphan Biovitrum (Sweden) · SENordland Hospital · NONorwegian University of Science and Technology · NOUniversity of Gothenburg · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMeconium aspiration syndrome (MAS) is a severe lung condition affecting newborns and it can lead to a systemic inflammatory response. We previously documented complement activation and cytokine release in a piglet MAS model. Additionally, we showed ex vivo that meconium-induced inflammation was dependent on complement and Toll-like receptors.

objectivesTo assess the efficacy of the combined inhibition of complement (C5) and CD14 on systemic inflammation induced in a forceful piglet MAS model.

methodsThirty piglets were randomly allocated to a treatment group receiving the C5-inhibitor SOBI002 and anti-CD14 (n = 15) and a nontreated control group (n = 15). MAS was induced by intratracheal meconium instillation, and the piglets were observed for 5 h. Complement, cytokines, and myeloperoxidase (MPO) were measured by ELISA.

resultsSOBI002 ablated C5 activity and the formation of the terminal complement complex in vivo. The combined inhibition attenuated the inflammasome cytokines IL-1β and IL-6 by 60 (p = 0.029) and 44% (p = 0.01), respectively, and also MPO activity in the bronchoalveolar fluid by 42% (p = 0.017). Ex vivo experiments in human blood revealed that the combined regimen attenuated meconium-induced MPO release by 64% (p = 0.008), but there was only a negligible effect with single inhibition, indicating a synergic cross-talk between the key molecules C5 and CD14.

conclusionCombined inhibition of C5 and CD14 attenuates meconium-induced inflammation in vivo and this could become a future therapeutic regimen for MAS.

Indexed as

AnimalsAnimals, NewbornComplement ActivationComplement C5CytokinesHumansInflammationLipopolysaccharide ReceptorsMeconiumMeconium Aspiration SyndromeRandom AllocationSwineComplement C5CytokinesLipopolysaccharide ReceptorsC5CD14ComplementInnate immunityMeconium aspiration syndromeSystemic inflammationToll-like receptor

Identifiers

PMID29486477
PMCPMC6008878
OpenAlexW2752563387

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.