The cytokine interleukin-1 (IL-1) is primarily to blame for a severe type of juvenile arthritis, according to Pascual and colleagues on page 1479. Blocking IL-1 activity in children with systemic onset juvenile idiopathic arthritis (SoJIA) completely resolved disease symptoms in a majority of children who had failed to respond to conventional treatments.

SoJIA is a systemic inflammatory disease of unknown etiology that can cause long-term arthritis in children. The pathogenesis of the disease is unclear, although increases in the inflammatory cytokine IL-6 have been reported in the blood of these patients. Currently the most effective therapy for SoJIA is long-term treatment with steroids, which carries with it the risk of growth retardation, osteoporosis, and obesity.

Pascual and colleagues now reveal a central role for IL-1—a cytokine that plays a major role in many inflammatory and autoimmune diseases—in the pathology of SoJIA. They show that serum from SoJIA patients provokes healthy cells to increase expression of IL-1, but no other cytokines. In addition, stimulated peripheral blood cells from children with SoJIA produced more IL-1, but not IL-6 or TNF, compared with cells from healthy children.

These results prompted Pascual and colleagues to treat these patients with an IL-1 receptor antagonist (Anakinra). The results were remarkable—symptoms were completely resolved or significantly improved in all children with active arthritis, with only one later case of reversion.

The mechanism behind the increased IL-1 production in SoJIA is unknown. As SoJIA is not an inherited disease, the defect is likely to be different from familial IL-1–triggered inflammatory diseases in which a mutated NALP3 can no longer control the activation of caspase-1, which cleaves the IL-1β precursor into the active cytokine. The authors are now looking for the serum component that turns on IL-1.