Objective Interleukin‐18 (IL‐18) is a proinflammatory cytokine that is involved in immunologically mediated tissue damage, but its bioactivity is regulated in vivo by its soluble decoy receptor, IL‐18 binding protein (IL‐18BP). This study was undertaken to determine levels of IL‐18 and IL‐18 binding inhibition in the blood of patients with adult‐onset Still's disease (ASD). Methods Serum concentrations of IL‐18 in ASD patients were compared by enzyme‐linked immunosorbent assay (ELISA) with those in patients with other systemic rheumatic diseases and healthy controls. The biologically active mature protein of IL‐18 was detected by Western blot analysis with anti–IL‐18 antibody and its induction of interferon‐γ (IFNγ) secretion from IL‐18–responding human myelomonocytic KG‐1 cells. The inhibitory activity on IL‐18 binding to its receptor was determined by 125I–IL‐18 binding inhibition assay using the Chinese hamster ovary cell line transfected with a murine IL‐18 receptor (CHO‐K1/mIL‐18R). Results Concentrations of serum IL‐18 were extremely elevated in patients with active ASD compared with those in patients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, polymyositis/dermatomyositis, Sjögren's syndrome, or healthy individuals. Levels of IL‐18 were found to correlate with serum ferritin values and disease severity in ASD. Western blot analysis revealed that serum samples from patients with active ASD contained an 18‐kd polypeptide of IL‐18, corresponding in size to the mature form. Accordingly, the samples were able to induce IFNγ secretion from KG‐1 cells, which was largely abolished by neutralizing anti–IL‐18 antibody. However, the level of IL‐18 bioactivity was more than 10‐fold weaker than the concentration of IL‐18 protein measured by ELISA. Serum samples from patients with active ASD showed an inhibitory effect on the binding of 125I–IL‐18 to CHO‐K1/mIL‐18R cells, and this activity was associated with elevation of IL‐18. Conclusion These data indicate that systemic overproduction of IL‐18 may be closely related to the pathogenesis of ASD, despite the restriction on its inflammatory activity by IL‐18 binding inhibitors such as IL‐18BP. The disease activity appears to be determined on the basis of the relative levels of IL‐18 and its specific inhibitors.

Objective. Interleukin-18 (IL-18) is a proinflammatory cytokine that is involved in immunologically mediated tissue damage, but its bioactivity is regulated in vivo by its soluble decoy receptor, IL-18 binding protein (IL-18BP). This study was undertaken to determine levels of IL-18 and IL-18 binding inhibition in the blood of patients with adult-onset Still's disease (ASD).Methods Conclusion. These data indicate that systemic overproduction of IL-18 may be closely related to the pathogenesis of ASD, despite the restriction on its inflammatory activity by IL-18 binding inhibitors such as IL-18BP. The disease activity appears to be determined on the basis of the relative levels of IL-18 and its specific inhibitors.

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Abstract. We here report a 77-year-old Japanese male who suffered general fatigue with progressive thirst and polyuria. Central diabetes insipidus was diagnosed by depletion of vasopressin secretion in response to increases in serum osmolality. Secretory responses of anterior pituitary hormones including adrenocorticotropin, thyrotropin, gonadotropins and growth hormone were severely impaired. Diffuse swelling of the infundibulum as well as lack of T1-hyperintense signal in the posterior lobe was noted by pituitary magnetic resonance imaging. The presence of bilateral hilar lymphadenopathy and increased CD4/CD8 ratio in bronchoalveolar lavage fluid was diagnostic for lung sarcoidosis. Physiological doses of corticosteroid and thyroid hormone were administered in addition to desmopressin supplementation. Complete regression of the neurohypophysial swelling was notable two years after corticosteroid replacement. Diffuse damage of anterior pituitary combined with hypothalamic involvement leading to central diabetes insipidus is a rare manifestation in such elderly patients with neurosarcoidosis.

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