Evidence map›Paper›PMID 21466684›Full record

ArticleCritical care (London, England)2011

Genetic variation of TLR4 influences immunoendocrine stress response: an observational study in cardiac surgical patients.

Alexander Koch, Lutz Hamann, Matthias Schott, Olaf Boehm, Dirk Grotemeyer, Muhammed Kurt, Carsten Schwenke, Ralf R Schumann, Stefan R Bornstein, Kai Zacharowski

Open access · goldAbstract read
In one paragraph

Article in Critical care (London, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

9 citing papers in PubMed, 11 citations in OpenAlex.

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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

10 authors at 8 institutions in 3 countries.

Alexander KochClinic of Anaesthesiology, Intensive Care Medicine and Pain Therapy, JW-Goethe-University Hospital, Theodor-Stern-Kai 7, Frankfurt am Main 60590, Germany. a.koch@med.uni-frankfurt.de
Lutz Hamann
Matthias Schott
Olaf Boehm
Dirk Grotemeyer
Muhammed Kurt
Carsten Schwenke
Ralf R Schumann
Stefan R Bornstein
Kai Zacharowski
Charité - Universitätsmedizin Berlin · DEDüsseldorf University Hospital · DEGoethe University Frankfurt · DEHôpital Kirchberg · LUStatistisches Bundesamt · DETU Dresden · DEUniversity Hospital Bonn · DEUniversity Hospital Frankfurt · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionSystemic inflammation (for example, following surgery) involves Toll-like receptor (TLR) signaling and leads to an endocrine stress response. This study aims to investigate a possible influence of TLR2 and TLR4 single nucleotide polymorphisms (SNPs) on perioperative adrenocorticotropic hormone (ACTH) and cortisol regulation in serum of cardiac surgical patients. To investigate the link to systemic inflammation in this context, we additionally measured 10 different cytokines in the serum.

methodsA total of 338 patients admitted for elective cardiac surgery were included in this prospective observational clinical cohort study. Genomic DNA of patients was screened for TLR2 and TLR4 SNPs. Serum concentrations of ACTH, cortisol, interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α and granulocyte macrophage-colony stimulating factor (GM-CSF) were determined before surgery, immediately post surgery and on the first postoperative day.

resultsThirteen patients were identified as TLR2 SNP carriers, 51 as TLR4 SNP carriers and 274 patients as non-carriers. Basal levels of ACTH, cortisol and cytokines did not differ among groups. In all three groups a significant, transient perioperative rise of cortisol could be observed. However, only in the non-carrier group this was accompanied by a significant ACTH rise. TLR4 SNP carriers had significant lower ACTH levels compared to non-carriers (mean (95% confidence intervals)) non-carriers: 201.9 (187.7 to 216.1) pg/ml; TLR4 SNP carriers: 149.9 (118.4 to 181.5) pg/ml; TLR2 SNP carriers: 176.4 ((110.5 to 242.3) pg/ml). Compared to non-carriers, TLR4 SNP carriers showed significant lower serum IL-8, IL-10 and GM-CSF peaks (mean (95% confidence intervals)): IL-8: non-carriers: 42.6 (36.7 to 48.5) pg/ml, TLR4 SNP carriers: 23.7 (10.7 to 36.8) pg/ml; IL-10: non-carriers: 83.8 (70.3 to 97.4) pg/ml, TLR4 SNP carriers: 54.2 (24.1 to 84.2) pg/ml; GM-CSF: non-carriers: 33.0 (27.8 to 38.3) pg/ml, TLR4 SNP carriers: 20.2 (8.6 to 31.8) pg/ml). No significant changes over time or between the groups were found for the other cytokines.

conclusionsRegulation of the immunoendocrine stress response during systemic inflammation is influenced by the presence of a TLR4 SNP. Cardiac surgical patients carrying this genotype showed decreased serum concentrations of ACTH, IL-8, IL-10 and GM-CSF. This finding might have impact on interpreting previous and designing future trials on diagnosing and modulating immunoendocrine dysregulation (for example, adrenal insufficiency) during systemic inflammation and sepsis.

Indexed as

Polymorphism, Single NucleotideAdrenocorticotropic HormoneAgedCardiac Surgical ProceduresFemaleGenotypeGranulocyte-Macrophage Colony-Stimulating FactorHumansHypothalamo-Hypophyseal SystemInflammationInterleukin-10Interleukin-8MaleMiddle AgedPerioperative PeriodPituitary-Adrenal SystemAdrenocorticotropic HormoneGranulocyte-Macrophage Colony-Stimulating FactorInterleukin-10Interleukin-8Toll-Like Receptor 2Toll-Like Receptor 4

Identifiers

PMID21466684
PMCPMC3219387
OpenAlexW2171099640

What OpenQuestion holds

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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.