Interleukin 6 as a therapeutic target in systemic-onset juvenile idiopathic arthritis.
OBJECTIVE
Systemic-onset juvenile idiopathic arthritis is a severe and steroid-dependent disease that sometimes progresses to a fatal disease, macrophage activation syndrome. The investigation of proinflammatory cytokine levels revealed the increases of interleukin 6 in serum of systemic-onset disease. To avoid the disease progression and the adverse events of high-dose corticosteroids, it might be a reasonable treatment strategy to inhibit the formation of interleukin 6/interleukin 6 receptor complex to block the binding to gp130 receptor, a biologically active receptor for interleukin 6.


RESULTS
Continuously elevated levels of interleukin 6 in serum may play an important role in manifesting the clinical symptoms and signs of systemic-onset juvenile idiopathic arthritis, including spiking fever, rash, arthritis, and serositis. The characteristic fever spikes parallel interleukin 6 levels. A long-term exposure of high levels of interleukin 6 brings children severe growth impairment, which was strongly suggested by the recent establishment of interleukin 6 transgenic mice.


CONCLUSIONS
This review will provide the evidences of the relation between the imbalance of interleukin 6 homeostasis and systemic-onset juvenile idiopathic arthritis. Also reviewed will be the author's recent trials of anti interleukin 6 receptor antibody, named temporally as MRA, for children with acute systemic disease intractable to long-term, high-dose, corticosteroid therapy. MRA would be a therapeutic modality for children with systemic-onset juvenile idiopathic arthritis intractable to high-dose corticosteroids.
Yokota
Shumpei
S
Department of Pediatrics, Yokohama City University School of Medicine, Kanagawa, Japan. syokota@med.yokohama-cu.ac.jp
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D000093242:Interleukin-6 Inhibitors