Clinical Correlates of Elevated Serum Levels of Interleukin-6 in Patients with Untreated Hodgkinʹs Disease

BACKGROUND: Interleukin-6 (IL-6) is a potent immunomodulatory cytokine that may have pathogenetic significance in several malignancies. In addition, high IL-6 levels have been associated with a poor prognosis in multiple myeloma, nonHodgkinʹs lymphoma, ovarian cancer, and renal cancer, as well in advanced Hodgkinʹs lymphoma. In this study, we analyzed IL-6 levels in newly diagnosed Hodgkinʹs disease and determined clinical correlates of elevated levels. PATIENTS AND METHODS: Using a sensitive enzyme-linked immunosorbent assay (lower limit of sensitivity = 0.35 pg/mL) we measured IL-6 levels in sera from 33 healthy controls and 65 untreated patients with Hodgkinʹs disease. RESULTS: Interleukin-6 levels in the Hodgkinʹs patients (median 2.7 pg/mL; range <0.35 to 38.4 pg/mL) were significantly higher than in the controls (median <0.35 pg/mL; range <0.35 to 1.87 pg/mL; P<0.0001). Interleukin-6 levels were also higher in males (P = 0.03) and in patients with bulky disease (P = 0.026) or advanced Ann Arbor stage (P = 0.017). In addition, serum levels of IL-6 also showed direct linear correlations with the erythrocyte sedimentation rate (r = 0.64, P = 0.0007), platelet count (r = 0.53, P<0.0001), leukocyte count (r = 0.36, P = 0.003), and β2-microglobulin level (r = 0.4, P = 0.0012); and an inverse linear correlation with serum albumin level (r = −0.43, P = 0.0003). In the 10 patients tested who had elevated serum IL-6 levels pretherapy and who achieved complete remission, serum IL-6 values decreased at the time of remission to the range found in healthy controls. CONCLUSIONS: Our observations suggest that, in patients with Hodgkinʹs disease, serum levels of IL-6 are frequently elevated at diagnosis, normalize during remission, and are associated with specific disease characteristics including several adverse prognostic features