Systemic-onset
juvenile idiopathic arthritis (JIA) is a severe and
steroid-dependent disease, which sometimes progresses to the fatal disease
macrophage activation syndrome. An investigation of inflammatory
cytokine levels revealed increases in
IL-6 in serum of systemic-onset disease patients. Continuously elevated levels of
IL-6 in serum may play a important role in manifesting the clinical symptoms and signs of systemic-onset JIA, including spiking
fever,
rash,
arthritis, and
serositis. The characteristic
fever spikes parallel
IL-6 levels. Long-term exposure to high levels of
IL-6 in children results in severe growth impairment, which was strongly suggested by the recent establishment of
IL-6 transgenic mice. To avoid
disease progression to
macrophage activation syndrome and the adverse effects of high-dose
corticosteroids, it might be reasonable to inhibit the formation of IL-6/IL-6R complex in order to block the binding to gp130 receptor, a biologically active receptor for
IL-6. This review will provide evidence of the relationship between
IL-6 homeostasis and systemic-onset JIA, and our recent trials of anti-IL-6R antibody (MRA) for children with acute systemic disease intractable to long-term and high-dose
corticosteroid therapy. MRA could be a therapeutic modality for children with systemic-onset JIA intractable to high-dose
corticosteroids.