Interleukin-6 and Soluble Interleukin-6 Receptor Levels as Markers of Disease Extent and Prognosis in Neuroblastoma

Purpose: To explore the relationships between interleukin-6 (IL-6) and soluble IL-6 receptor (slL-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.