Serum levels of IL-6 type cytokines and soluble IL-6 receptors in active B-cell chronic lymphocytic leukemia and in cladribine induced remission

Abstract

We have investigated the serum concentrations of interleukin‐6 (IL‐6) and two IL‐6 family cytokines‐oncostatin M (OSM) and leukemia inhibitory factor (LIF)‐in 63 patients with B‐cell chronic lymphocytic leukemia (B‐CLL) and 17 healthy controls using the enzyme‐linked immunosorbent assay (ELISA) method. Simultaneously, we measured the serum levels of the soluble forms of two subunits of the IL‐6 receptor complex‐ligand binding glycoprotein 80 (sIL‐6R) and glycoprotein 130 (sgp130). The cytokines and receptors were evaluated in 25 untreated patients and 38 patients treated with cladribine (2‐CdA), as well as in 17 healthy controls. We have correlated the serum levels of these proteins with Rai′s clinical stage of the disease, the response to 2‐CdA treatment and some hematological parameters. We have also evaluated the correlation of the IL‐6 serum level with the concentration of OSM and IL‐6 soluble receptors. IL‐6 was measurable in 62/63 (98.4%), OSM in 20/25 (80%) of untreated and 14/38 (37.8%) of the treated patients. sIL‐6R and sgp130 were detectable in all 63 patients and LIF in none of the CLL patients. IL‐6 serum level in untreated patients was not significantly different as compared to its concentration in the control group (P > 0.05). However, in the patients treated with 2‐CdA the IL‐6 level was significantly lower (P < 0.02), and the lowest concentration was found in the patients with complete remission (CR; median 1.4 pg/ml; P < 0.02). The concentration of sIL‐6R was significantly higher in untreated (median 61.8 ng/ml) and treated (median 50.1 ng/ml) CLL patients when compared to normal persons (median 41.2 ng/ml; P = 0.04; P < 0.001, respectively). There was no difference between the sIL‐6R levels in the patients with CR and the healthy controls. In non‐responders sIL‐6R concentration was the highest and similar to its level in the untreated patients. OSM level was higher in the untreated patients (median 1.8 pg/ml) than in the normal controls (median 0.0 pg/ml; P < 0.001) and in the CR patients (median 0.0 pg/ml; P < 0.03). The serum concentration of sgp130 was similar in the untreated (median 480 pg/ml) and treated (median 470 pg/ml) patients, as well as in the healthy persons (median 420 pg/ml; P > 0.05). We have found significant positive correlation between the levels of sIL6R and the lymphocytes count in CLL patients (Ρ=0.423; P < 0.001). In addition, sIL‐6R and OSM serum concentrations correlated also with CLL Rai stage. In conclusion, the serum level of IL‐6, OSM and sIL‐6R, but not LIF and sgp130, are useful indicators of CLL activity.