hemophagocytic syndrome Severe imbalance of IL-18/IL-18BP in patients with secondary

ABSTRACT Hemophagocytic syndrome (HPS) is characterized by an uncontrolled and poorly understood activation of Th-1 lymphocytes and macrophages. We studied 20 patients with HPS secondary to infections, autoimmune disease, lymphoma, or cancer and observed that the concentrations of serum IL-18, a strong inducer of Th-1 responses, IFN-γ production, stimulation of macrophages and NK cells was highly increased in HPS but not in control patients. In contrast, concentrations of its natural inhibitor, the IL-18 binding protein, were only moderately elevated, resulting in a high level of biologically active free IL-18 in HPS (4.6 fold increase compared with controls, P<0.001). Free IL-18 but not IL-12 concentrations significantly correlated with clinical status and the biological markers of HPS such as anemia (P<0.001), hypertriglyceridemia and hyperferritinemia (P<0.01), and also with markers of Th-1 lymphocyte or macrophage activation such as elevated concentrations of IFN-γ, soluble IL-2 and TNFα receptors concentrations. Despite high IL-18 elevation, in vitro NK cell cytotoxicity was severely impaired in HPS patients, in part due to NK cell lymphopenia which was observed in a majority of patients, but also secondary to an intrinsic NK cell functional deficiency. We concluded that a severe IL-18/IL-18BP imbalance results in Th-1 lymphocyte and macrophage activation which escape control by NK cell cytotoxicity and may allow for secondary HPS in patients with underlying diseases.From bloodjournal.hematologylibrary.org by guest on June 2, 2013. For personal use only.

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