Cytokine Profiles of Macrophage Activation Syndrome Associated with Rheumatic Diseases

Objective. To elucidate the cytokine profiles of macrophage activation syndrome (MAS) in relation to underlying rheumatic diseases and prognosis. Methods. The clinical features and laboratory data of 18 patients with MAS and rheumatic diseases were retrospectively analyzed. Serum levels of macrophage colony-stimulating factor (M-CSF), interleukin 18 (IL-18), tumor necrosis factor-α, interleukin 6, interferon-γ, ferritin, and ß 2 -microglobulin (ß 2 m) were measured. These data were compared between underlying diseases and between those who died and those who recovered. Results. Of the 18 patients with MAS, 9 had underlying systemic lupus erythematosus (SLE), 7 had adult-onset Still’s disease (AOSD), 1 had rheumatoid arthritis (RA), and 1 had antiphospholipid syndrome. Three patients with SLE and 1 patient with RA died. The serum M-CSF and IL-18 levels were substantially elevated in all the patients. In the patients with SLE, the M-CSF level was higher than the IL-18 level (median: 4879 vs 1341 pg/ml, p = 0.0054), and it was the reverse in the patients with AOSD (5883 vs 228,350 pg/ml, p = 0.0017). The serum M-CSF and ß 2 m levels were significantly higher in the patients who died than in those who recovered (M-CSF: 18,245 vs 3404 pg/ml, p = 0.019; ß 2 m: 18.8 vs 5.4 mg/dl, p = 0.0058). Conclusion. The cytokine profiles associated with MAS differed between patients with SLE and patients with AOSD. The patients with SLE showed a prominent increase in serum M-CSF levels, as did the patients with AOSD in serum IL-18 level. Patients who died had higher serum M-CSF and ß 2 m levels, and this suggests that aggressive treatment for patients with MAS and these profiles should be promptly started.