Background Adult onset Still¡¯s disease (AOSD) is a systemic inflammatory disease in adults. The clinical and laboratory findings of AOSD are well known, however, the cause and pathophysiology of AOSD are scarcely understood. One characteristic finding of AOSD is a reticuloendothelial system activation, which is showed up as lymphadenopathy, hepatosplenomegaly, elevated serum ferritin levels, and combined hemophagocytic syndrome in severe cases.
Objectives To figure out the cytokine network in AOSD, we measured the levels of serum cytokines related to macrophages which is major cell in reticuloendothelial system.
Methods The subjects of the present study were 19 patients diagnosed with AOSD according to Yamaguchi criteria from 1998.6 to 2000.3. Sixty-three serial blood samples were obtained from these nineteen AOSD patients (male:5, female:14) and also blood samples were obtained from age- and sex-matched 16 healthy adults as controls. Serum levels of tumour necrosis factor-α(TNF-α), interleukin-1b (IL-1b), interferon-γ(INF-γ), interleukin-12 (IL-12), interleukin-12 p40 (IL-12 p40), interleukin-15(IL-15), and interleukin-18(IL-18) were measured by the ELISA method. Serum ferritin and C-reactive protein levels were measured by nephelometry. Regression analysis (mixed effect model) was used to correct the effect of serial samples in each individual.
Results Mean age of AOSD patients was 35.5¡¾11.3 years. Nine patients had serious clinical courses which demanded more than once steroid pulse therapy and/or cyclophosphamide therapy. Four cases had died despite having received intensive care (3: disseminated intravascular coagulation (DIC) and shock, 1: heart failure), and hemophagocytic syndrome was confirmed by bone marrow biopsy in one pancytopenic patient. Serum levels of IL-1b, IL-12 p40, IL-15, IL-18, TNF-α, and INF-γ were significantly higher in AOSD patients. INF-γ levels well correlated with serum ferritin levels that reflect the disease activity of AOSD. The cytokines that correlated with INF-γ were IL-18 and TNF-α, not IL-12 or IL-15. IL-18 levels well correlated with INF-γ, but it did not correlate with TNF-α and ferritin levels.
Conclusion Macrophage related cytokines were activated in AOSD patients. INF-γ levels correlated with serum ferritin levels, and the activation pathway of INF-γ in AOSD was thought to be through IL-18, not IL-12 or IL-15.
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