Interleukin-6 and soluble interleukin-6 receptor levels as markers of disease extent and prognosis in neuroblastoma

Clin Cancer Res. 2008 Nov 1;14(21):7028-34. doi: 10.1158/1078-0432.CCR-07-5017.


Purpose: To explore the relationships between interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) levels and disease extent and clinical outcome in childhood neuroblastoma.

Experimental design: Pretreatment peripheral blood (PB; n=53) and bone marrow (n=18) samples from patients with neuroblastoma were assayed by ELISA for IL-6 and sIL-6R. PB values were compared with healthy pediatric controls (n=28).

Results: PB IL-6 levels were significantly elevated in patients with high-risk disease compared with those with low and intermediate risk disease (23.9 versus 4.3 pg/mL; P<0.001) and the normal control group (23.9 versus 3.3 pg/mL; P<0.001). Similarly, bone marrow IL-6 levels were higher in high-risk patients when compared with low- and intermediate-risk patients (15 versus 0 pg/mL; P<0.02). Other factors correlated with higher IL-6 levels were age of >18 months, bony metastases, and unfavorable histology. sIL-6R levels were not significantly correlated with disease stage. Patients with detectable PB IL-6 at diagnosis had significantly lower event-free survival rates (P<0.008). sIL-6R levels <2.5 x 10(4) pg/mL were also associated with a significantly worse event-free survival (P=0.016).

Conclusion: Elevated PB IL-6 levels correlated with features of high-risk neuroblastoma and poor prognosis in this population. Decreased PB sIL-6R levels correlated with the presence of metastatic disease. Further study of these markers in children with neuroblastoma seems warranted.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Bone Marrow / chemistry
  • Disease-Free Survival
  • Female
  • Humans
  • Infant
  • Interleukin-6 / analysis*
  • Interleukin-6 / blood
  • Male
  • Neuroblastoma / diagnosis
  • Neuroblastoma / metabolism*
  • Prognosis
  • Receptors, Interleukin-6 / analysis*
  • Receptors, Interleukin-6 / blood


  • Biomarkers, Tumor
  • Interleukin-6
  • Receptors, Interleukin-6