Identifying specific roles for individual cytokines is complicated by the observation that they share common functional subunits. Interleukin-12 (IL-12) is a heterodimer of p35 and p40 subunits, and is thought to be important in T-cell-dependent immunity and inflammation. In the February 13 Nature, Daniel Cua and colleagues report that IL-23 — a heterodimer of the IL-12 p40 subunit together with a distinct p19 subunit — may be a more important factor in autoimmune inflammation (Nature, 421:744-748, February 13, 2003).

Cua et al. used knockout mice and cytokine replacement studies to address the role of the p19, p35 or p40 subunits in experimental autoimmune encephalomyelitis (EAE) — an inflammatory disease model. IL-23, but not IL-12, was essential for the development of EAE. IL-23 directly activated macrophages in vivo, inducing cytokine expression and late-stage inflammation.

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