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[HDL inhibit cytokine production in a mouse model of urate crystal-induced inflammation]
A Scanu1, F Oliviero, R Luisetto
1Cattedra e U.O.C. di Reumatologia, Università di Padova, Padova, Italia. anna.scanu@unipd.it
Objectives:
To evaluate whether high density lipoproteins (HDL) affect monosodium urate (MSU) crystal-induced inflammation in the murine air pouch model.
Methods:
MSU crystals were prepared by Denko's method and sterilized by heating at 180°C for 2 h before each experiment. Human HDL were isolated from peripheral blood of healthy volunteers. MSU crystals (2 mg in 1 ml of PBS) were injected into subcutaneous air pouches in mice in the presence or absence of HDL (0.1 mg). Negative control pouches received 1 ml of PBS. To recover pouch fluid, the pouches were washed with 2 ml of PBS after the animals were sacrificed. The leukocyte count in the lavage fluids was obtained using a hemocytometer and differential leukocyte count was determined by May-Grunwald-Giemsa staining. IL-6, KC, CCL2 and TNF-α levels were measured in exudates by ELISA.
Results:
MSU crystals increased the number of leukocytes and the neutrophil migration, as well as the concentrations of IL-6, KC and CCL2 in pouch fluids, while the TNF-α levels were not detectable. The treatment with HDL led to a reduction in all inflammatory parameters: the leukocyte count decreased by 73%; the neutrophil density decreased by 35%; the IL-6, KC and CCL2 concentration decreased by 4-, 6- and 5-fold respectively.
Conclusions:
This study shows that HDL may limit the inflammatory process by inhibiting leukocyte recruitment and cytokine release. HDL are likely to represent a mechanism of control of crystal-induced inflammation.
Insights
High-density lipoproteins (HDL) significantly reduce inflammation caused by monosodium urate (MSU) crystals in mice. HDL limits leukocyte recruitment and inflammatory cytokine release, suggesting a role in controlling crystal-induced inflammation.
Area of Science:
- Biochemistry
- Immunology
- Inflammation Research
Context:
- Gout is a painful inflammatory arthritis caused by monosodium urate (MSU) crystal deposition.
- The role of high-density lipoproteins (HDL) in modulating MSU crystal-induced inflammation is not fully understood.
- Understanding inflammatory pathways is crucial for developing effective gout treatments.
Purpose:
- To investigate the effect of HDL on MSU crystal-induced inflammation in a murine air pouch model.
- To quantify changes in leukocyte count, neutrophil migration, and cytokine levels following HDL treatment.
- To determine if HDL can inhibit key inflammatory mediators involved in gout pathogenesis.
Summary:
- MSU crystals induced significant leukocyte influx, neutrophil migration, and elevated levels of IL-6, KC, and CCL2 in the air pouch.
- Administration of HDL markedly reduced leukocyte count (73%) and neutrophil density (35%).
- HDL treatment also led to substantial reductions in IL-6 (4-fold), KC (6-fold), and CCL2 (5-fold) concentrations.
Impact:
- HDL demonstrates potent anti-inflammatory properties against MSU crystal-induced inflammation.
- HDL may serve as a therapeutic agent for managing gout and other crystal-induced inflammatory conditions.
- These findings highlight a novel mechanism by which HDL exerts protective effects in inflammatory arthritis.
