Evidence map›Paper›PMID 31819009›Full record

ArticleThe Journal of biological chemistry2020

PASylation of IL-1 receptor antagonist (IL-1Ra) retains IL-1 blockade and extends its duration in mouse urate crystal-induced peritonitis.

Nicholas E Powers, Benjamin Swartzwelter, Carlo Marchetti, Dennis M de Graaf, Alexandra Lerchner, Martin Schlapschy, Rajiv Datar, Uli Binder, Carl K Edwards, Arne Skerra and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

18 citing papers in PubMed, 18 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

11 authors at 3 institutions in 3 countries.

Nicholas E PowersDepartment of Medicine, University of Colorado, Aurora, Colorado 80045 nicholas.e.powers@CUAnschutz.edu.ORCID 0000-0002-5403-4324
Benjamin SwartzwelterDepartment of Medicine, University of Colorado, Aurora, Colorado 80045.ORCID 0000-0002-6283-5199
Carlo MarchettiDepartment of Medicine, University of Colorado, Aurora, Colorado 80045.ORCID 0000-0002-4184-2234
Dennis M de GraafDepartment of Medicine, University of Colorado, Aurora, Colorado 80045.ORCID 0000-0002-9198-7159
Alexandra LerchnerXL-protein GmbH, Lise-Meitner-Strasse 30, 85354 Freising, Germany.
Martin SchlapschyLehrstuhl für Biologische Chemie, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising, Germany.
Rajiv DatarDNX Biopharmaceuticals, Inc., San Diego, California 92121.
Uli BinderXL-protein GmbH, Lise-Meitner-Strasse 30, 85354 Freising, Germany.
Carl K EdwardsDNX Biopharmaceuticals, Inc., San Diego, California 92121.ORCID 0000-0002-7353-0200
Arne SkerraLehrstuhl für Biologische Chemie, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising, Germany.ORCID 0000-0002-5717-498X
Charles A DinarelloDepartment of Medicine, University of Colorado, Aurora, Colorado 80045.ORCID 0000-0002-5073-8316
University of Colorado Anschutz Medical Campus · USRadboud University Nijmegen · NLTechnical University of Munich · DE

Funding

Yeast-based HTS Assay Technologies for ProteasesR01AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 1985 to 2025
$8.5M
Pathogenesis of Fever in ManR56AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 2016 to 2016
$311k
NIAID NIH HHS R01 AI015614NIAID NIH HHS R56 AI015614
6 · The paper itself

Abstract

Interleukin-1 (IL-1) is a key mediator of inflammation and immunity. Naturally-occurring IL-1 receptor antagonist (IL-1Ra) binds and blocks the IL-1 receptor-1 (IL-1R1), preventing signaling. Anakinra, a recombinant form of IL-1Ra, is used to treat a spectrum of inflammatory diseases. However, anakinra is rapidly cleared from the body and requires daily administration. To create a longer-lasting alternative, PASylated IL-1Ra (PAS-IL-1Ra) has been generated by in-frame fusion of a long, defined-length, N-terminal Pro/Ala/Ser (PAS) random-coil polypeptide with IL-1Ra. Here, we compared the efficacy of two PAS-IL-1Ra molecules, PAS600-IL-1Ra and PAS800-IL-1Ra (carrying 600 and 800 PAS residues, respectively), with that of anakinra in mice. PAS600-IL-1Ra displayed markedly extended blood plasma levels 3 days post-administration, whereas anakinra was undetectable after 24 h. We also studied PAS600-IL-1Ra and PAS800-IL-1Ra for efficacy in monosodium urate (MSU) crystal-induced peritonitis. 5 days post-administration, PAS800-IL-1Ra significantly reduced leukocyte influx and inflammatory markers in MSU-induced peritonitis, whereas equimolar anakinra administered 24 h before MSU challenge was ineffective. The 6-h pretreatment with equimolar anakinra or PAS800-IL-1Ra before MSU challenge similarly reduced inflammatory markers. In cultured A549 lung carcinoma cells, anakinra, PAS600-IL-1Ra, and PAS800-IL-Ra reduced IL-1α-induced IL-6 and IL-8 levels with comparable potency. In human peripheral blood mononuclear cells, these molecules suppressed

Indexed as

AnimalsBiomarkersHumansInflammationInterleukin-1Interleukin 1 Receptor Antagonist ProteinLeukocytesMicePeritonitisUric AcidBiomarkersIl1rn protein, mouseInterleukin-1Interleukin 1 Receptor Antagonist ProteinUric Acidbiotechnologydrug deliveryhalf-life extensionIL-22inflammationinnate immunityinterleukin 1 (IL-1)intrinsically-disordered proteinleukocytePASylationpharmacokinetics

Identifiers

PMID31819009
PMCPMC6970921
OpenAlexW2996518466

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.