Increased interleukin-18 levels in patients with hemophagocytic lymphohistiocytosis

Purpose: Clinical characteristics of HLH is associated with overproduction of cytokines. Th1 type cytokines, IFN-γ, TNF-α are detected in high levels in the serum of patients and are possibly associated with the clinical manifestations. To elucidate the mechanism of the Th1 type cytokine overproduction, we analyzed the IL-18 levels in the serum of HLH patients. Materials and Methods: Sera were obtained from HLH patients. All patients had persistent high-grade fever, hepatosplenomegaly, liver dysfunction, pancytopenia, hyperferritinemia, coagulopathy and hemophagocytosis in the bone marrow. Serum IL-18 levels were assayed by EIA. Results: Serum IL-18 levels were elevated in 9 of the 9 patients (814 -10900 pg/ml in patients compared with 153-331 pg/ml in healthy controls) during the active phase of the disease. The serum IL-18 levels in HLH patients were significantly higher than those of the patients with infectious mononucleosis (p<0.05). Conclusions: It is reported that serum IL-12 levels are elevated in patients with HLH. IL-18 must also be an important factor in the pathogenesis of HLH. IL-18, in concern with IL-12 from monocytes/macrophages, may strongly induce IFN^y, Th1 type cytokines which stimulate monocytes/macrophages.