Diagnostic accuracy of a specific cytokine pattern in hemophagocytic lymphohistiocytosis in children

J Pediatr. 2012 Jun;160(6):984-90.e1. doi: 10.1016/j.jpeds.2011.11.046. Epub 2012 Jan 9.


Objective: The study goal was to determine the diagnostic accuracy of a specific cytokine pattern including interferon-gamma (IFN-γ), interleukin (IL)-10, and IL-6 for hemophagocytic lymphohistiocytosis (HLH) in febrile children.

Study design: In this prospective study, 756 patients with fever admitted to a hematology-oncology unit were enrolled. The causes of fever were documented and the serum cytokines, including IFN-γ, tumor necrosis factor-alpha (TNF-α), IL-10, IL-6, IL-4, and IL-2, were determined using cytometric bead array techniques.

Results: Of 1474 episodes of fever that were analyzed, 71 episodes of HLH manifested a specific cytokine pattern of highly increased levels of IFN-γ (median level: 1088.5 pg/mL) and IL-10 (623.5 pg/mL) but a moderately increased level of IL-6 (51.1 pg/mL). IL-6 was predominantly increased to varied extents in patients in the sepsis group (244.6 pg/mL) and the nonsepsis infection group (34.7 pg/mL). The diagnostic accuracy of IFN-γ and IL-10 for HLH was 99.5% and 92.8%, respectively. By applying the cutoff point of 100 pg/mL, IFN-γ had a sensitivity of 94.4% and a specificity of 97.2% for HLH. When using the criteria of IFN-γ >75 pg/mL and IL-10 >60 pg/mL, the specificity reached 98.9% and the sensitivity was 93.0%.

Conclusions: The specific cytokine pattern of markedly elevated levels of IFN-γ and IL-10 with only modestly elevated IL-6 levels has high diagnostic accuracy for HLH and may be a useful approach to differentiate HLH from infection.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Cytokines / blood*
  • Diagnosis, Differential
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Infant, Newborn
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Interleukin-6 / blood
  • Lymphohistiocytosis, Hemophagocytic / blood
  • Lymphohistiocytosis, Hemophagocytic / diagnosis*
  • Male
  • Prospective Studies
  • Reproducibility of Results
  • Tumor Necrosis Factor-alpha / blood


  • Biomarkers
  • Cytokines
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma