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Contribution of mast cell-derived interleukin-1? to uric acid crystal-induced acute arthritis in mice.

ABSTRACT: Gouty arthritis is caused by the precipitation of monosodium urate monohydrate (MSU) crystals in the joints. While it has been reported that mast cells (MCs) infiltrate gouty tophi, little is known about the actual roles of MCs during acute attacks of gout. This study was undertaken to assess the role of MCs in a mouse model of MSU crystal-induced acute arthritis.We assessed the effects of intraarticular (IA) injection of MSU crystals in various strains of mice with constitutive or inducible MC deficiency or in mice lacking interleukin-1? (IL-1?) or other elements of innate immunity. We also assessed the response to IA injection of MSU crystals in genetically MC-deficient mice after IA engraftment of wild-type or IL-1?(-/-) bone marrow-derived cultured MCs.MCs were found to augment acute tissue swelling following IA injection of MSU crystals in mice. IL-1? production by MCs contributed importantly to MSU crystal-induced tissue swelling, particularly during its early stages. Selective depletion of synovial MCs was able to diminish MSU crystal-induced acute inflammation in the joints.Our findings identify a previously unrecognized role of MCs and MC-derived IL-1? in the early stages of MSU crystal-induced acute arthritis in mice.

SUBMITTER: Reber LL

PROVIDER: S-EPMC4443497 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Contribution of mast cell-derived interleukin-1β to uric acid crystal-induced acute arthritis in mice.

Reber Laurent L LL Marichal Thomas T Sokolove Jeremy J Starkl Philipp P Gaudenzio Nicolas N Iwakura Yoichiro Y Karasuyama Hajime H Schwartz Lawrence B LB Robinson William H WH Tsai Mindy M Galli Stephen J SJ

Arthritis & rheumatology (Hoboken, N.J.) 20141001 10

<h4>Objective</h4>Gouty arthritis is caused by the precipitation of monosodium urate monohydrate (MSU) crystals in the joints. While it has been reported that mast cells (MCs) infiltrate gouty tophi, little is known about the actual roles of MCs during acute attacks of gout. This study was undertaken to assess the role of MCs in a mouse model of MSU crystal-induced acute arthritis.<h4>Methods</h4>We assessed the effects of intraarticular (IA) injection of MSU crystals in various strains of mice ...[more]

PMID: 24943488

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Project description:Rationale & objectiveUric acid is excreted by the kidney and accumulates in acute kidney injury (AKI). Whether higher plasma uric acid level predisposes to AKI or its complications is not known.Study designProspective observational cohort study.Setting & participants2 independent cohorts of critically ill patients: (1) 208 patients without AKI admitted to the intensive care unit (ICU) at Brigham & Women's Hospital between October 2008 and December 2016; and (2) 250 participants with AKI requiring renal replacement therapy (RRT) who had not yet initiated RRT enrolled in the Acute Renal Failure Trial Network (ATN) Study.ExposurePlasma uric acid level upon ICU admission and before RRT initiation in the ICU and ATN Study cohorts, respectively.OutcomesIncident AKI and 60-day mortality in the ICU and ATN Study cohorts, respectively.Analytical approachLogistic regression models were used to test the association of plasma uric acid level with incident AKI and 60-day mortality.ResultsIn the ICU cohort, median plasma uric acid level was 4.7 (interquartile range [IQR], 3.6-6.4) mg/dL, and 40 patients (19.2%) developed AKI. Higher plasma uric acid levels associated with incident AKI, but this association was confounded by serum creatinine level and was not significant after multivariable adjustment (adjusted OR per doubling of uric acid, 1.50; 95% CI, 0.80-2.81). In the ATN Study cohort, median plasma uric acid level was 11.1 (IQR, 8.6-14.2) mg/dL, and 125 participants (50.0%) died within 60 days. There was no statistically significant association between plasma uric acid levels and 60-day mortality in either unadjusted models or after multivariable adjustment for demographic, severity-of-illness, and kidney-specific covariates (adjusted OR per doubling of uric acid, 1.15; 95% CI, 0.71-1.86).LimitationsHeterogeneity of ICU patients.ConclusionsPlasma uric acid levels upon ICU admission or before RRT initiation are not independently associated with adverse clinical outcomes in critically ill patients.

Dataset Information

Contribution of mast cell-derived interleukin-1? to uric acid crystal-induced acute arthritis in mice.

Publications

Contribution of mast cell-derived interleukin-1β to uric acid crystal-induced acute arthritis in mice.

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