Abstract
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.
Highlights
Acute gout is a common cause of arthritis, affecting approximately 1% of the adult population, and epidemiological evidence suggests that its prevalence is increasing [1]
The monosodium urate (MSU) crystals trigger IL-1 release through innate immune pathways, which include TLR-2 and TLR-4, found on the surface of monocytes and macrophages, as well as the 'inflammasome' complex that leads to IL-1β activation [5,6]
As treatment with drugs currently used in acute gout is not always well tolerated or is contraindicated due to coexistent medical problems, we investigated the validity of IL-1 blockade as therapy in acute gout
Summary
Acute gout is a common cause of arthritis, affecting approximately 1% of the adult population, and epidemiological evidence suggests that its prevalence is increasing [1]. Current treatments during an acute attack include nonsteroidal antiinflammatory drugs (NSAIDs), colchicine and corticosteroids. These agents are generally effective, they present significant risks in patients who have pre-existing renal, cardiovascular and gastrointestinal diseases. Among the many cytokines implicated [2,3], IL-1 may have a special role in the inflammatory network, as MSU crystals stimulate IL-1 release by monocytes and synovial mononuclear cells [4]. The MSU crystals trigger IL-1 release through innate immune pathways, which include TLR-2 and TLR-4, found on the surface of monocytes and macrophages, as well as the 'inflammasome' complex that leads to IL-1β activation [5,6]. The inflammasome acts as an intracellular sensor of inflammatory stimuli and regulates the activation of caspase-1
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