Increased interleukin‐18 expression in bone marrow of a patient with systemic juvenile idiopathic arthritis and unrecognized macrophage‐activation syndrome

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Abstract
The aberrant induction of proinflammatory cytokines is considered to be crucial in the pathogenesis of systemic juvenile idiopathic arthritis and adult‐onset Still's disease. Interleukin‐18 (IL‐18) in particular has been reported to be a candidate for the key cytokine in both diseases; however, the origin of IL‐18 is unclear. To clarify the origin, we investigated specimens from various organs obtained during autopsy of a child with systemic JIA and macrophage activation syndrome, using immunohistochemical staining. Our results showed a high number of cells expressing IL‐18 in the bone marrow but not in the other organs. This finding suggests that bone marrow is the origin of increased serum IL‐18 and raises the possibility that other proinflammatory cytokines are also induced by IL‐18 in bone marrow in this disease. Bone marrow may be an essential organ in the pathogenesis of systemic JIA.

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