Background: Gout is an inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in tissues. It is well known to be mediated via the activation of the NLRP3 inflammasomes. Auranofin, FDA-approved anti-rheumatic drug, has demonstrated potent inhibition of NLRP3 inflammasomes activation in various cell types.

Objectives: This study aims to investigate whether auranofin can modulate MSU-induced NLRP3 inflammasomes activation in gout and alleviate inflammation associated with the disease.

Methods: Male C57BL/6 mice were administered with Auranofin (10 mg/kg, 20 mg/kg) or colchicine (1 mg/kg, as a positive control) intraperitoneally, once daily for 5 weeks. To induce gout arthritis, MSU crystals (30 mg/mL) were injected into the footpad and the tissues samples were collected 24 hours post-injection. For the air pouch model, MSU crystals (3 mg/mL) were injected into a subcutaneous air pouch created on the back of the mice. Six hours after injection, the air pouch lavage fluids were harvested for analysis.

Results: Auranofin alleviated gout arthritis represented by reduced foot thickness and decreased expression of pro-inflammatory cytokines in the foot tissue addressed by PCR and immunoblotting. Further, the levels of pro-inflammatory cytokines such as IL-1β, IL-18, TNF-a and myeloperoxidase activity in air pouch exudates, were significantly lower in auranofin-treated group. Consistently, flow cytometry analysis revealed auranofin a decreased percentage of neutrophils in the treated group. Additionally, auranofin suppressed the expression of CXCL1, a chemokine involved in neutrophil migration. Notably, auranofin reduced the expression of IL-33, a pro-inflammatory cytokine that regulates the expression of CXCL1.

Conclusion: Auranofin alleviates gout inflammation by suppressing the production of pro-inflammatory cytokines and inhibiting neutrophil migration in an IL-33/ST2-dependent manner. Additionally, given its demonstrated efficacy in treating fatty liver, auranofin shows promise as a potent anti-inflammatory drug for gout management.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.