A pilot study of IL-1 inhibition by anakinra in acute gout.
Monosodium urate crystals stimulate monocytes and macrophages to release IL-1beta 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.
So
Alexander
A
Service of Rhumatologie, Department of Medicine, Centre Hospitalier Universtaire Vaudois and University of Lausanne, 1011 Lausanne, Switzerland. AlexanderKai-Lik.So@chuv.ch
De Smedt
Thibaut
T
Revaz
Sylvie
S
Tschopp
Jürg
J
D000328:Adult; D000368:Aged; D000818:Animals; D015210:Arthritis, Gouty / Q000188:drug therapy*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy; D010865:Pilot Projects; D014527:Uric Acid / Q000633:toxicity
D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D014527:Uric Acid