Such a biphasic model is attractive and certainly would explain: (1) the observation that many children with sJIA begin with severe systemic features that can then evolve over months or years to a more chronic arthritis phenotype (6, 7); (2) the effectiveness of IL-1 blockade in some patients, particularly early in the disease (8); and (3) the propensity to macrophage activation syndrome (MAS), driven initially by IL-1 and IL-18, which in turn activate interferon-gamma (INF-γ) and IL-2 production from activated CD8 lymphocytes (9). The gene discussed is IL1B; the disease is macrophage activation syndrome.