Altered Levels of Interleukin-lp and Interleukin-l Receptor Antagonist in Chronic Myelogenous Leukemia: Clinical and Prognostic Correlates

We have recently demonstrated that interleukin (IL)-lp levels are elevated in advanced chronic myelogenous leukemia CML) and that IL-l inhibitors can suppress CML clonogenic growth. To further assess the clinical implications of increased IL-1p expression in CML, we analyzed IL-1p and ILl receptor antagonist (IL-IRA) levels in leukocyte lysates from a series of CML patients and from normal volunteers. Both IL-1s and IL-IRA were measured by enzyme-linked immunosorbent assays (ELISAS), with the lower limits of ensitivity of the assays being 20 pg/mL and 6.5 pg/mL, respectively. The median IL-1p level in the 81 CML patients tested was higher (115.8 pg/2.4 x I O 7 cells; range, 0 to 2,000 pg/ 2.4 x lo7 cells) than the median level in 25 control samples (10.8 pg/2.4 x I O 7 cells; range, 0 t o 95.5 pg/2.4 x I O 7 cells) ( P < . O I L IL-1p was bioactive, as demonstrated with a bioassay based on cytotoxicity to a melanoma cell line (A375). For survival analysis, elevated IL-1p levels were defined as those exceeding the mean + 2 SD of normal levels (83 pg/2.4 x I O 7 cells). The survival of the 44 patients with elevated IL18 levels was significantly shorter than that of those who had low IL-10 levels (median, 44 W 58 months; P = .049 by