Spontaneous Resolution of Acute Gout: Mechanisms and Therapeutic Targets

Overview

Journal RMD Open

Publisher BMJ Publishing Group

Specialty Rheumatology

Date 2023 Sep 21

PMID 37734872

Authors

Meiling Shi

Jiao Luo

Liting Ding

Lihua Duan

Affiliations

Soon will be listed here.

Abstract

Gout is a common inflammatory arthritis that has been increasing in both prevalence and incidence. Consequently, management of refractory and chronic gout has been gaining attention. Onset of gout is related to the deposition of monosodium urate crystals under hyperuricaemia. Interestingly, acute gout attacks often resolve spontaneously within 7-10 days, and many studies have confirmed the notion that gout flares can be self-relieved. However, the underlying mechanism for spontaneous remission of gout requires further elucidation. In this article, we summarise the roles and mechanisms related to spontaneous remission of gout, which are essential for understanding its pathogenesis and developing potential targeted therapies.

Citing Articles

Constructing a machine learning model for systemic infection after kidney stone surgery based on CT values.

Li J, Du Y, Huang G, Huang Y, Xi X, Ye Z Sci Rep. 2025; 15(1):4327.

PMID: 39910162 PMC: 11799361. DOI: 10.1038/s41598-025-88704-y.

The pathogenesis of gout.

Ahn E, So M J Rheum Dis. 2024; 32(1):8-16.

PMID: 39712248 PMC: 11659655. DOI: 10.4078/jrd.2024.0054.

Resolution of acute inflammation induced by monosodium urate crystals (MSU) through neutrophil extracellular trap-MSU aggregate-mediated negative signaling.

Lu C, Shen C, Li K, Wu C, Chen Y, Kuo Y J Inflamm (Lond). 2024; 21(1):50.

PMID: 39605016 PMC: 11604016. DOI: 10.1186/s12950-024-00423-9.

Hyperuricemia and its related diseases: mechanisms and advances in therapy.

Du L, Zong Y, Li H, Wang Q, Xie L, Yang B Signal Transduct Target Ther. 2024; 9(1):212.

PMID: 39191722 PMC: 11350024. DOI: 10.1038/s41392-024-01916-y.

Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Alleviates Inflammatory Joint Pain in Osteoarthritis and Gouty Arthritis Preclinical Models.

Freeze R, Hughes P, Haystead T, Scarneo S J Pain Res. 2024; 17:2287-2298.

PMID: 38952995 PMC: 11216608. DOI: 10.2147/JPR.S451409.

References

Duan L, Luo J, Fu Q, Shang K, Wei Y, Wang Y . Decreased Expression of CD14 in MSU-Mediated Inflammation May Be Associated with Spontaneous Remission of Acute Gout. J Immunol Res. 2019; 2019:7143241. PMC: 6595337. DOI: 10.1155/2019/7143241. View

Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J . Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006; 440(7081):237-41. DOI: 10.1038/nature04516. View

Steiger S, Harper J . Neutrophil cannibalism triggers transforming growth factor β1 production and self regulation of neutrophil inflammatory function in monosodium urate monohydrate crystal-induced inflammation in mice. Arthritis Rheum. 2013; 65(3):815-23. DOI: 10.1002/art.37822. View

Schlesinger N, Alten R, Bardin T, Schumacher H, Bloch M, Gimona A . Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis. 2012; 71(11):1839-48. DOI: 10.1136/annrheumdis-2011-200908. View

Tausche A, Richter K, Grassler A, Hansel S, Roch B, Schroder H . Severe gouty arthritis refractory to anti-inflammatory drugs: treatment with anti-tumour necrosis factor alpha as a new therapeutic option. Ann Rheum Dis. 2004; 63(10):1351-2. PMC: 1754753. DOI: 10.1136/ard.2003.015743. View

Mitroulis I, Kambas K, Ritis K . Neutrophils, IL-1β, and gout: is there a link?. Semin Immunopathol. 2013; 35(4):501-12. DOI: 10.1007/s00281-013-0361-0. View

Desai J, Steiger S, Anders H . Molecular Pathophysiology of Gout. Trends Mol Med. 2017; 23(8):756-768. DOI: 10.1016/j.molmed.2017.06.005. View

Mabrey F, Nian H, Yu C, Barnes E, Malhotra U, Mikacenic C . Phase 2, randomized, double-blind, placebo-controlled multi-center trial of the clinical and biological effects of anti-CD14 treatment in hospitalized patients with COVID-19 pneumonia. EBioMedicine. 2023; 93:104667. PMC: 10276526. DOI: 10.1016/j.ebiom.2023.104667. View

Scott P, Ma H, Viriyakosol S, Terkeltaub R, Liu-Bryan R . Engagement of CD14 mediates the inflammatory potential of monosodium urate crystals. J Immunol. 2006; 177(9):6370-8. DOI: 10.4049/jimmunol.177.9.6370. View

10.

Mulay S, Desai J, Kumar S, Eberhard J, Thomasova D, Romoli S . Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis. Nat Commun. 2016; 7:10274. PMC: 4738349. DOI: 10.1038/ncomms10274. View

11.

Shang K, Wei Y, Su Q, Yu B, Tao Y, He Y . IL-33 Ameliorates the Development of MSU-Induced Inflammation Through Expanding MDSCs-Like Cells. Front Endocrinol (Lausanne). 2019; 10:36. PMC: 6399133. DOI: 10.3389/fendo.2019.00036. View

12.

Onuora S . IL-37 linked to gout pathogenesis and treatment. Nat Rev Rheumatol. 2020; 16(5):250. DOI: 10.1038/s41584-020-0410-8. View

13.

Wu Z, Zhang Z, Lei Z, Lei P . CD14: Biology and role in the pathogenesis of disease. Cytokine Growth Factor Rev. 2019; 48:24-31. DOI: 10.1016/j.cytogfr.2019.06.003. View

14.

Saag K, Khanna P, Keenan R, Ohlman S, Osterling Koskinen L, Sparve E . A Randomized, Phase II Study Evaluating the Efficacy and Safety of Anakinra in the Treatment of Gout Flares. Arthritis Rheumatol. 2021; 73(8):1533-1542. DOI: 10.1002/art.41699. View

15.

Yokose K, Sato S, Asano T, Yashiro M, Kobayashi H, Watanabe H . TNF-α potentiates uric acid-induced interleukin-1β (IL-1β) secretion in human neutrophils. Mod Rheumatol. 2017; 28(3):513-517. DOI: 10.1080/14397595.2017.1369924. View

16.

Janssen C, Oude Voshaar M, Vonkeman H, Jansen T, Janssen M, Kok M . Anakinra for the treatment of acute gout flares: a randomized, double-blind, placebo-controlled, active-comparator, non-inferiority trial. Rheumatology (Oxford). 2019; . DOI: 10.1093/rheumatology/key402. View

17.

Zhang Y, Pan R, Xu Y, Zhao Y . Treatment of refractory gout with TNF-α antagonist etanercept combined with febuxostat. Ann Palliat Med. 2020; 9(6):4332-4338. DOI: 10.21037/apm-20-2072. View

18.

Schauer C, Janko C, Munoz L, Zhao Y, Kienhofer D, Frey B . Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nat Med. 2014; 20(5):511-7. DOI: 10.1038/nm.3547. View

19.

Alves-Filho J, Sonego F, Souto F, Freitas A, Verri Jr W, Auxiliadora-Martins M . Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection. Nat Med. 2010; 16(6):708-12. DOI: 10.1038/nm.2156. View