A pilot study of IL-1 inhibition by anakinra in acute gout

By A. So, T. de Smedt, S. Revaz, J. Tschopp. Arthritis Research & Therapy, 2007

749 citations recorded by the source corpus.

Monosodium urate crystals stimulate monocytes and macrophages to release IL-1β through the NALP3 component of the inflammasome. The effectiveness of IL-1 inhibition in hereditary autoinflammatory syndromes with mutations in the NALP3 protein suggested that IL-1 inhibition might also be effective in relieving the inflammatory manifestations of acute gout. The effectiveness of IL-1 inhibition was first evaluated in a mouse model of monosodium urate crystal-induced inflammation. IL-1 inhibition prevented peritoneal neutrophil accumulation but TNF blockade had no effect. Based on these findings, we performed a pilot, open-labeled study (trial registration number ISRCTN10862635) in 10 patients with gout who could not tolerate or had failed standard antiinflammatory therapies. All patients received 100 mg anakinra daily for 3 days. All 10 patients with acute gout responded rapidly to anakinra. No adverse effects were observed. IL-1 blockade appears to be an effective therapy for acute gouty arthritis. The clinical findings need to be confirmed in a controlled study.

Subfields: Molecular Biology, Nephrology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/898e409ddc5b2dbd5a4c7a92a44d06f5b8caca35

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. C. A. Dinarello
2. J. Tschopp
3. G. Núñez
4. Kate Schroder
5. E. Latz
6. Fabio Martinon
7. Annick Mayor
8. L. Franchi

In Nephrology

1. J. Tschopp
2. Kate Schroder
3. C. A. Dinarello
4. G. Núñez
5. H. Kono
6. K. Rock
7. E. Latz
8. Hyon K. Choi

In Public Health, Environmental and Occupational Health

1. C. A. Dinarello
2. G. Núñez
3. Kate Schroder
4. J. Tschopp

Citations in the corpus

• Caspase functions in cell death and disease. (2013, background): “For example, patients with gout, pseudogout, or pulmonary silicosis have shown great improvement after treatment with an IL-1b antagonist (McGonagle et al. 2007, 2008; So et al. 2007; Terkeltaub et al. 2009).”
• Sterile inflammation: sensing and reacting to damage (2010, background): “Anakinra was shown to be highly effective in the treatment of patients with gout who could not tolerate or did not respond to previous therap”
• The inflammasomes: guardians of the body. (2009, background): “Similarly, patients with pseudogout, an inflammatory disease caused by the deposition of calcium pyrophosphate dihydrate crystals (CPPD), another type of pathogenic microcrystal that activates the NALP3 inflammasome (8), responded well to treatment with the IL-1ra (124).”
• Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*). (2009, background): “Small pilot studies of anakinra suggest that this research is translatable into the clinic (131, 132).”
• Anti-inflammatory Agents: Present and Future (2010, positive): “Common Diseases Mediated by IL-1β Urate Crystal Arthritis (gout) (So et al., 2007; Terkeltaub et al., 2009) Type 2 Diabetes (Donath et al.”
• The Inflammasome: A Caspase-1 Activation Platform Regulating Immune Responses and Disease Pathogenesis (2009, background): “Consistent with that observation, patients with gouty attacks improve clinically when treated with IL-1Ra, a molecule that inhibits IL-1R signalin”
• 2012 American College of Rheumatology Guidelines for Management of Gout Part I: Systematic Non-pharmacologic and Pharmacologic Therapeutic Approaches to Hyperuricemia (2012, neutral): “However, there was no specific TFP vote on the question of avoidance of excess purine intake from food sources other than meat and seafood, such as vegetables and legumes, in gout patients (44).”
• IL‐1, IL‐18, and IL‐33 families of cytokines (2008, background): “Blockade of IL-1b by treatment with anakinra led to rapid resolution of episodes of acute gout in 10 patients who had failed standard anti-inflammatory therapies (35).”
• NLRP3 inflammasome: From a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases (2015, background): “…LRR, leucine-rich-repeat olymorphonuclear leukocytes; POP, PYD-only proteins; PRRs, pattern-recognition MCs, smooth muscle cells; TLRs, toll-like receptors; TNF, tumor necrosis factor; Trx, unfolded protein response eing Biology (B2A), UMR-8256/INSERM ERL-1164, Université Pierre et Marie Curie,”
• The sterile inflammatory response (2010, methodology): “Supporting this idea, patients that are treated with IL-1ra have only a very small increase in the incidence of infections (113)((88, 114); although it remains to be seen if this becomes a greater problem with agents that may block IL-1 responses more effectively than IL-1ra.”
• The IL-1 family: regulators of immunity (2010, background): “Indeed, pilot clinical studies using anakinra showed considerable benefi”