Early diagnostic and prognostic significance of a specific Th1/Th2 cytokine pattern in children with haemophagocytic syndrome

Br J Haematol. 2008 Oct;143(1):84-91. doi: 10.1111/j.1365-2141.2008.07298.x. Epub 2008 Jul 31.


The haemophagocytic syndrome (HPS) is a rare but frequently fatal disorder of immune regulation caused by hypercytokinemia. Using cytometric bead array technique, the serum T-helper cell type 1 (Th1) and 2 (Th2) cytokines including interferon-gamma (IFN-gamma), tumour necrosis factor (TNF), interleukin (IL)-10, IL-6, IL-4 and IL-2 were determined in 24 children with de novo HPS and 87 children as control. The median levels of serum IFN-gamma, IL-10 and IL-6 in the acute phase of HPS were 901.7, 879.0 and 63.8 pg/ml, respectively, significantly higher than those after remission, and in the healthy volunteers and patients with viral infection. IL-4 was slightly elevated while IL-2 and TNF were within normal range in acute phase. Patients with bacterial sepsis showed an extremely high level of IL-6 and moderate level of IL-10, whereas IFN-gamma was only slightly elevated. Five patients were diagnosed with HPS according to the Th1/Th2 cytokine pattern 3-13 d earlier than they fulfilled the relevant diagnostic criteria. IL-10 level >2000 pg/ml was an unfavorable prognostic factor for HPS treatment response (P = 0.033) and outcome (P = 0.009). We conclude that the significant increase of IFN-gamma and IL-10 and a slightly increased level of IL-6 is an early, specific and prognostic cytokine pattern for childhood HPS.

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • Case-Control Studies
  • Chi-Square Distribution
  • Child
  • Child, Preschool
  • Cytokines / blood*
  • Female
  • Humans
  • Infant
  • Interferon-gamma / immunology
  • Interleukin-10 / immunology
  • Interleukin-2 / immunology
  • Interleukin-4 / immunology
  • Interleukin-6 / immunology
  • Kaplan-Meier Estimate
  • Lymphohistiocytosis, Hemophagocytic / diagnosis*
  • Lymphohistiocytosis, Hemophagocytic / immunology
  • Lymphohistiocytosis, Hemophagocytic / mortality
  • Male
  • Prognosis
  • Survival Analysis
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*
  • Tumor Necrosis Factor-alpha / immunology


  • Biomarkers
  • Cytokines
  • Interleukin-2
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma