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


ABSTRACT:

Background

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.

Methods

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.

Results

OLT1177 reduced zymosan-induced joint swelling (p ?0.0001), which was associated with decreased synovial IL-1?, IL-6, myeloperoxidase, and CXCL1 levels (p?ConclusionsOral OLT1177 is highly effective in ameliorating reactive as well as gouty arthritis.

SUBMITTER: Marchetti C 

PROVIDER: S-EPMC6091035 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Marchetti Carlo C   Swartzwelter Benjamin B   Koenders Marije I MI   Azam Tania T   Tengesdal Isak W IW   Powers Nick N   de Graaf Dennis M DM   Dinarello Charles A CA   Joosten Leo A B LAB  

Arthritis research & therapy 20180803 1


<h4>Background</h4>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.<h4>Methods</h4>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 infiltra  ...[more]

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