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NLRP3 inflammasome inhibitor OLT1177 suppresses joint inflammation in murine models of acute arthritis

Overview of attention for article published in Arthritis Research & Therapy, August 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (84th percentile)
  • Good Attention Score compared to outputs of the same age and source (71st percentile)

Mentioned by

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1 news outlet
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1 X user
wikipedia
1 Wikipedia page

Citations

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111 Dimensions

Readers on

mendeley
88 Mendeley
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1 CiteULike
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Title
NLRP3 inflammasome inhibitor OLT1177 suppresses joint inflammation in murine models of acute arthritis
Published in
Arthritis Research & Therapy, August 2018
DOI 10.1186/s13075-018-1664-2
Pubmed ID
Authors

Carlo Marchetti, Benjamin Swartzwelter, Marije I. Koenders, Tania Azam, Isak W. Tengesdal, Nick Powers, Dennis M. de Graaf, Charles A. Dinarello, Leo A. B. Joosten

Abstract

Activation of the NLRP3 inflammasome in gout amplifies the inflammatory response and mediates further damage. In the current study, we assessed the therapeutic effect of OLT1177, an orally active NLRP3 inflammasome inhibitor that is safe in humans, in murine acute arthritis models. Zymosan or monosodium urate (MSU) crystals were injected intra-articularly (i.a.) into mouse knee joints to induce reactive or gouty arthritis. Joint swelling, articular cell infiltration, and synovial cytokines were evaluated 25 hours and 4 hours following zymosan or MSU challenge, respectively. OLT1177 was administrated intraperitoneally by oral gavage or in the food by an OLT1177-enriched diet. OLT1177 reduced zymosan-induced joint swelling (p < 0.001), cell influx (p < 0.01), and synovial levels of interleukin (IL)-1β, IL-6, and chemokine (C-X-C motif) ligand 1 (CXCL1) (p < 0.05), respectively, when compared with vehicle-treated mice. Plasma OLT1177 levels correlated (p < 0.001) dose-dependently with reduction in joint inflammation. Treatment of mice with OLT1177 limited MSU crystal articular inflammation (p > 0.0001), which was associated with decreased synovial IL-1β, IL-6, myeloperoxidase, and CXCL1 levels (p < 0.01) compared with vehicle-treated mice. When administrated orally 1 hour after MSU challenge, OLT1177 reduced joint inflammation, processing of IL-1β, and synovial phosphorylated c-Jun N-terminal kinase compared with the vehicle group. Mice were fed an OLT1177-enriched diet for 3 weeks and then challenged i.a. with MSU crystals. Joint swelling, synovial IL-1β, and expression of Nlrp3 and Il1b were significantly reduced in synovial tissues in mice fed an OLT1177-enriched diet when compared with the standard diet group. Oral OLT1177 is highly effective in ameliorating reactive as well as gouty arthritis.

X Demographics

X Demographics

The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 88 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 88 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 13 15%
Student > Master 8 9%
Researcher 8 9%
Student > Bachelor 7 8%
Student > Doctoral Student 6 7%
Other 10 11%
Unknown 36 41%
Readers by discipline Count As %
Medicine and Dentistry 9 10%
Biochemistry, Genetics and Molecular Biology 7 8%
Pharmacology, Toxicology and Pharmaceutical Science 5 6%
Agricultural and Biological Sciences 4 5%
Immunology and Microbiology 4 5%
Other 18 20%
Unknown 41 47%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 13. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 December 2020.
All research outputs
#2,657,080
of 25,385,509 outputs
Outputs from Arthritis Research & Therapy
#526
of 3,381 outputs
Outputs of similar age
#52,225
of 341,622 outputs
Outputs of similar age from Arthritis Research & Therapy
#19
of 69 outputs
Altmetric has tracked 25,385,509 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,381 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one has done well, scoring higher than 84% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 341,622 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 84% of its contemporaries.
We're also able to compare this research output to 69 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.