Evidence map›Paper›PMID 18591229›Full record

ArticleInfection and immunity2008

Stages of meningococcal sepsis simulated in vitro, with emphasis on complement and Toll-like receptor activation.

Bernt Christian Hellerud, Jørgen Stenvik, Terje Espevik, John D Lambris, Tom Eirik Mollnes, Petter Brandtzaeg

Open access · greenAbstract read
In one paragraph

Article in Infection and immunity, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

21 citing papers in PubMed, 40 citations in OpenAlex.

  1. Frontiers in cellular and infection microbiology · 2023
    Article
  2. Article
  3. Journal of immunology research · 2019
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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

6 authors at 4 institutions in 2 countries.

Bernt Christian HellerudDepartment of Pediatrics, Ullevål University Hospital, and University of Oslo, Oslo, Norway. b.c.hellerud@medisin.uio.no
Jørgen Stenvik
Terje Espevik
John D Lambris
Tom Eirik Mollnes
Petter Brandtzaeg
Norwegian University of Science and Technology · NOUniversity of Oslo · NOOslo University Hospital · NOUniversity of Pennsylvania · US

Funding

Role of complement in kidney disorders: from hemodialysis to transportationP01AI068730 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI LAMBRIS, JOHN D · 2007 to 2018
$16.0M
STRUCTURAL-FUNCTIONAL ANALYSIS OF COMPSTATINR01GM062134 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI LAMBRIS, JOHN D · 2001 to 2010
$2.5M
NIAID NIH HHS AI-068730NIAID NIH HHS P01 AI068730NIGMS NIH HHS GM-62134NIGMS NIH HHS R01 GM062134
6 · The paper itself

Abstract

The clinical presentation of meningococcal disease is closely related to the number of meningococci in the circulation. This study aimed to examine the activation of the innate immune system after being exposed to increasing and clinically relevant concentrations of meningococci. We incubated representative Neisseria meningitidis serogroup B (ST-32) and serogroup C (ST-11) strains and a lipopolysaccharide (LPS)-deficient mutant (the 44/76 lpxA mutant) in human serum and whole blood and measured complement activation and cytokine secretion and the effect of blocking these systems. HEK293 cells transfected with Toll-like receptors (TLRs) were examined for activation of NF-kappaB. The threshold for cytokine secretion and activation of NF-kappaB was 10(3) to 10(4) meningococci/ml. LPS was the sole inflammation-inducing molecule at concentrations up to 10(5) to 10(6) meningococci/ml. The activation was dependent on TLR4-MD2-CD14. Complement contributed to the inflammatory response at >or=10(5) to 10(6) meningococci/ml, and complement activation increased exponentially at >or=10(7) bacteria/ml. Non-LPS components initiated TLR2-mediated activation at >or=10(7) bacteria/ml. As the bacterial concentration exceeded 10(7)/ml, TLR4 and TLR2 were increasingly activated, independent of CD14. In this model mimicking human disease, the inflammatory response to N. meningitidis was closely associated with the bacterial concentration. Therapeutically, CD14 inhibition alone was most efficient at a low bacterial concentration, whereas addition of a complement inhibitor may be beneficial when the bacterial load increases.

Indexed as

Cell LineComplement ActivationComplement System ProteinsCytokinesHumansLipopolysaccharidesNeisseria meningitidisNF-kappa BSepsisToll-Like ReceptorsComplement System ProteinsCytokinesLipopolysaccharidesNF-kappa BToll-Like Receptors

Identifiers

PMID18591229
PMCPMC2519403
OpenAlexW2118117236

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.