Evidence map›Paper›PMID 25907631›Full record

ArticleClinical and experimental immunology2015

The anti-inflammatory effect of combined complement and CD14 inhibition is preserved during escalating bacterial load.

Kjetil H Egge, Andreas Barratt-Due, Stig Nymo, Julie K Lindstad, Anne Pharo, Corinna Lau, Terje Espevik, Ebbe B Thorgersen, Tom E Mollnes

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and experimental immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

7 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. 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

9 authors at 4 institutions in 1 country.

Kjetil H EggeDepartment of Immunology, Oslo University Hospital Rikshospitalet, and K. G. Jebsen IRC, University of Oslo, Oslo, Norway.
Andreas Barratt-DueDepartment of Immunology, Oslo University Hospital Rikshospitalet, and K. G. Jebsen IRC, University of Oslo, Oslo, Norway.
Stig NymoResearch Laboratory, Nordland Hospital and Faculty of Health Sciences, K. G. Jebsen TREC, University of Tromsø, Tromsø, Norway.
Julie K LindstadDepartment of Immunology, Oslo University Hospital Rikshospitalet, and K. G. Jebsen IRC, University of Oslo, Oslo, Norway.
Anne PharoDepartment of Immunology, Oslo University Hospital Rikshospitalet, and K. G. Jebsen IRC, University of Oslo, Oslo, Norway.
Corinna LauResearch Laboratory, Nordland Hospital and Faculty of Health Sciences, K. G. Jebsen TREC, University of Tromsø, Tromsø, Norway.
Terje EspevikCentre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Ebbe B ThorgersenDepartment of Immunology, Oslo University Hospital Rikshospitalet, and K. G. Jebsen IRC, University of Oslo, Oslo, Norway.
Tom E MollnesDepartment of Immunology, Oslo University Hospital Rikshospitalet, and K. G. Jebsen IRC, University of Oslo, Oslo, Norway.
University of Oslo · NONordland Hospital · NONorwegian University of Science and Technology · NOOslo University Hospital · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Combined inhibition of complement and CD14 is known to attenuate bacterial-induced inflammation, but the dependency of the bacterial load on this effect is unknown. Thus, we investigated whether the effect of such combined inhibition on Escherichia coli- and Staphylococcus aureus-induced inflammation was preserved during increasing bacterial concentrations. Human whole blood was preincubated with anti-CD14, eculizumab (C5-inhibitor) or compstatin (C3-inhibitor), or combinations thereof. Then heat-inactivated bacteria were added at final concentrations of 5 × 10(4) -1 × 10(8) /ml (E. coli) or 5 × 10(7) -4 × 10(8) /ml (S. aureus). Inflammatory markers were measured using enzyme-linked immunosorbent assay (ELISA), multiplex technology and flow cytometry. Combined inhibition of complement and CD14 significantly (P < 0.05) reduced E. coli-induced interleukin (IL)-6 by 40-92% at all bacterial concentrations. IL-1β, IL-8 and macrophage inflammatory protein (MIP)-1α were significantly (P < 0.05) inhibited by 53-100%, and the effect was lost only at the highest bacterial concentration. Tumour necrosis factor (TNF) and MIP-1β were significantly (P < 0.05) reduced by 80-97% at the lowest bacterial concentration. Monocyte and granulocyte CD11b were significantly (P < 0.05) reduced by 63-91% at all bacterial doses. Lactoferrin was significantly (P < 0.05) attenuated to the level of background activity at the lowest bacterial concentration. Similar effects were observed for S. aureus, but the attenuation was, in general, less pronounced. Compared to E. coli, much higher concentrations of S. aureus were required to induce the same cytokine responses. This study demonstrates generally preserved effects of combined complement and CD14 inhibition on Gram-negative and Gram-positive bacterial-induced inflammation during escalating bacterial load. The implications of these findings for future therapy of sepsis are discussed.

Indexed as

Antibodies, Monoclonal, HumanizedAntibodies, NeutralizingBacterial LoadCD11b AntigenComplement C3Complement C5CytokinesEnzyme-Linked Immunosorbent AssayEscherichia coliFlow CytometryGranulocytesHot TemperatureHumansInflammationLipopolysaccharide ReceptorsMonocytesAntibodies, Monoclonal, HumanizedAntibodies, NeutralizingCD11b AntigenComplement C3Complement C5compstatinCytokineseculizumabLipopolysaccharide ReceptorsPeptides, CyclicCD14complementinflammationsepsis

Identifiers

PMID25907631
PMCPMC4557382
OpenAlexW2148538851

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.