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

Abstract

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.

Figure 1

Inhibition of monosodium urate-induced peritoneal neutrophil influx by anti-IL-1 treatment. (a) BALB/C mice were injected intraperitoneally with 0.5 mg monosodium urate (MSU) crystals together with PBS or anti-IL-1RI mAb (200 μg) or anakinra (200 μg). (b) BALB/C mice were injected intraperitoneally with 0.5 mg MSU crystals together with PBS or anti-TNF mAb (200 μg) or anakinra (200 μg). Neutrophil influx in the peritoneum was quantified 6 hours later. Values are the mean ± standard error of the mean of five mice per group. An unpaired Student's t test was used to calculate the P value.