Evidence map›Paper›PMID 25713100›Full record

Trial reportJournal of lipid research2015

IL-6 blockade by monoclonal antibodies inhibits apolipoprotein (a) expression and lipoprotein (a) synthesis in humans.

Nike Müller, Dominik M Schulte, Kathrin Türk, Sandra Freitag-Wolf, Jochen Hampe, Rainald Zeuner, Johann O Schröder, Ioanna Gouni-Berthold, Heiner K Berthold, Wilhelm Krone and 3 more

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

Trial report in Journal of lipid research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 4 pooled it
6.4field-weighted citation impact, top 3% 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

96 citing papers in PubMed, 4 syntheses or guidelines pooled it, 155 citations in OpenAlex.

  1. Pooled it
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  4. Pooled it
  5. Trial
  6. Trial
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  8. Article
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  15. Article
  16. The biology of lipoprotein(a): From genetics to molecular mechanisms.European journal of clinical investigation · 2026
    Review
  17. Review
  18. Article
  19. Article
  20. Inflammation, Lp(a) and cardiovascular mortality: results from the LURIC study.Clinical research in cardiology : official journal of the German Cardiac Society · 2025
    Article

36 more citing papers are in PubMed but not listed here.

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

13 authors at 5 institutions in 1 country.

Nike MüllerDepartment I of Internal Medicine, University of Kiel, Kiel, Germany.
Dominik M SchulteDepartment I of Internal Medicine, University of Kiel, Kiel, Germany Cluster of Excellence Inflammation at Interfaces, University of Kiel, Kiel, Germany.
Kathrin TürkDepartment I of Internal Medicine, University of Kiel, Kiel, Germany.
Sandra Freitag-WolfInstitute of Medical Informatics and Statistics, University of Kiel, Kiel, Germany.
Jochen HampeDepartment of Medicine I, University Hospital Carl Gustav Carus, University of Dresden, Dresden, Germany.
Rainald ZeunerDepartment I of Internal Medicine, University of Kiel, Kiel, Germany.
Johann O SchröderDepartment I of Internal Medicine, University of Kiel, Kiel, Germany Cluster of Excellence Inflammation at Interfaces, University of Kiel, Kiel, Germany.
Ioanna Gouni-BertholdCenter for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany.
Heiner K BertholdDepartment of Internal Medicine and Geriatrics, Bielefeld Evangelical Hospital, Bielefeld, Germany.
Wilhelm KroneCenter for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany.
Stefan Rose-JohnCluster of Excellence Inflammation at Interfaces, University of Kiel, Kiel, Germany Institute of Biochemistry, University of Kiel, Kiel, Germany.
Stefan SchreiberDepartment I of Internal Medicine, University of Kiel, Kiel, Germany Cluster of Excellence Inflammation at Interfaces, University of Kiel, Kiel, Germany.
Matthias LaudesDepartment I of Internal Medicine, University of Kiel, Kiel, Germany Cluster of Excellence Inflammation at Interfaces, University of Kiel, Kiel, Germany.
Kiel University · DECluster of Excellence "Inflammation at Interfaces"University of Cologne · DEEvangelisches Krankenhaus Bielefeld · DEUniversity Hospital Carl Gustav Carus · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lipoprotein (a) [Lp(a)] is a highly atherogenic lipid particle. Although earlier reports suggested that Lp(a) levels are mostly determined by genetic factors, several recent studies have revealed that Lp(a) induction is also caused by chronic inflammation. Therefore, we aimed to examine whether cytokine blockade by monoclonal antibodies may inhibit Lp(a) metabolism. We found that interleukin 6 (IL-6) blockade by tocilizumab (TCZ) reduced Lp(a) while TNF-α-inhibition by adalimumab in humans had no effect. The specificity of IL-6 in regulating Lp(a) was further demonstrated by serological measurements of human subjects (n = 1,153) revealing that Lp(a) levels are increased in individuals with elevated serum IL-6. Transcriptomic analysis of human liver biopsies (n = 57) revealed typical IL-6 response genes being correlated with the LPA gene expression in vivo. On a molecular level, we found that TCZ inhibited IL-6-induced LPA mRNA and protein expression in human hepatocytes. Furthermore, examination of IL-6-responsive signal transducer and activator of transcription 3 binding sites within the LPA promoter by reporter gene assays, promoter deletion experiments, and electrophoretic mobility shift assay analysis showed that the Lp(a)-lowering effect of TCZ is specifically mediated via a responsive element at -46 to -40. Therefore, IL-6 blockade might be a potential therapeutic option to treat elevated Lp(a) serum concentrations in humans and might be a noninvasive alternative to lipid apheresis in the future.

Indexed as

Interleukin-6 InhibitorsAdalimumabAntibodies, Monoclonal, HumanizedAntirheumatic AgentsApoprotein(a)Arthritis, RheumatoidFemaleHep G2 CellsHumansInterleukin-6LiverMaleMiddle AgedProtein BiosynthesisResponse ElementsSTAT3 Transcription FactorAdalimumabAntibodies, Monoclonal, HumanizedAntirheumatic AgentsApoprotein(a)IL6 protein, humanInterleukin-6Interleukin-6 InhibitorsSTAT3 protein, humanSTAT3 Transcription Factortocilizumabacute phase responseinflammationinterleukinlipoprotein metabolismtherapy of elevated Lp(a)

Identifiers

PMID25713100
PMCPMC4409280
OpenAlexW2161655722

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.