Affordable Access

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

  • Karin Mazodier
  • Valérie Marin
  • Daniela Novick
  • Catherine Farnarier
  • Stéphane Robitail
  • Nicolas Schleinitz
  • Véronique Veit
  • Pascale Paul
  • Menachem Rubinstein
  • Charles A. Dinarello
  • Jean-Robert Harlé
  • Gilles Kaplanski
The American Society of Hematology
Publication Date
Nov 15, 2005
  • Biology
  • Medicine


Hemophagocytic syndrome (HPS) is characterized by an uncontrolled and poorly understood activation of T-helper 1 (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 interleukin 18 (IL-18), a strong inducer of Th-1 responses, interferon γ (IFN-γ) production, and stimulation of macrophages and natural killer (NK) cells were highly increased in HPS but not in control patients. In contrast, concentrations of its natural inhibitor, the IL-18 binding protein (IL-18BP), 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 < .001). Free IL-18 but not IL-12 concentrations significantly correlated with clinical status and the biologic markers of HPS such as anemia (P < .001), hypertriglyceridemia, and hyperferritinemia (P < .01) and also with markers of Th-1 lymphocyte or macrophage activation, such as elevated concentrations of IFN-γ and soluble IL-2 and tumor necrosis factor α (TNF-α) receptor concentrations. Despite high IL-18 elevation, in vitro NK-cell cytotoxicity was severely impaired in HPS patients, in part due to NK-cell lymphopenia that 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 escapes control by NK-cell cytotoxicity and may allow for secondary HPS in patients with underlying diseases.

Report this publication


Seen <100 times