Systemic-onset
juvenile idiopathic arthritis (sJIA) is a severe and
steroid-dependent disease of unknown etiology that sometimes progresses to a fatal disease known as the
macrophage activation syndrome. The investigation of inflammatory
cytokines and receptor levels revealed an increase in
interleukin (IL)-6 and soluble
IL-6 receptor (sIL-6R) in serum of patients with active sJIA. The clinical symptoms and signs of the disease are presumably attributable to the continuous elevation of
IL-6 and sIL-6R levels in serum. The characteristic
fever spikes parallel
IL-6 levels. In children, a long-term exposure to high levels of
IL-6 causes severe growth impairment, as suggested by recently established studies of
IL-6 transgenic mice. The biological functions of
IL-6 are expressed through the binding of IL-6/IL-6R complex to gp130. The administration of
tocilizumab (a recombinant humanized anti-IL-6R
monoclonal antibody) exerts its action by preventing the binding of
IL-6 to its receptor and, therefore, preventing the activation of gp130. After a few cases of compassionate use of
tocilizumab, phase I and II studies of
tocilizumab were conducted in children with sJIA, revealing that
tocilizumab abruptly reduced the typical symptoms of
inflammation and improved laboratory abnormalities. This article describes the experience in Japan regarding the treatment of sJIA with
tocilizumab and supports the hypothesis that high levels of
IL-6 may play an important role in the pathogenesis and maintenance of this disease. A confirmation of the role of
tocilizumab in the treatment of sJIA will be provided by the results of the ongoing phase III study in Japan.