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

WE have investigated the serum concentrations of interleukin-6 (IL-6) and t wo IL-6 family cytokines-oncostatin M (OSM) and leukemia inhibitory factor (LIF)-in 63 patients with B-cell chronic lymphocytic leukemia (B-CLL) and 1 7 healthy controls using the enzyme-linked immunosorbent assay (ELISA) meth od. Simultaneously, we measured the serum levels of the soluble forms of tw o subunits of the IL-6 receptor complex-ligand binding glycoprotein 80 (sIL -6R) and glycoprotein 130 (sgp130). The cytokines and receptors were evalua ted 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 o f these proteins with Rai's clinical stage of the disease, the response to 2-CdA treatment and some hematological parameters. We have also evaluated t he 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 (8 0%) of untreated and 14/38 (37.8%) of the treated patients. sIL-6R and sgp1 30 were detectable in ail 63 patients and LIF in none of the CLL patients. IL-6 serum level in untreated patients was not significantly different as c ompared 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 hi the patients with complete rem ission (CR; median 1.4 pg/ml; P<0.02). The concentration of sIL-6R was sign ificantly 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 lev els hi 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 pat ients (median 0.0 pg/ml; P<0.03). The serum concentration of sgp130 was sim ilar in the untreated (median 480 pg/ml) and treated (median 470 pg/ml) pat ients, as well as in the healthy persons (median 420 pg/ml; P>0.05). We hav e found significant positive correlation between the levels of sIL-6R and t he lymphocytes count in CLL patients (rho=0.423; P<0.001). In addition, sIL -6R and OSM serum concentrations correlated also with CLL Rai stage. In con clusion, the serum level of IL-6, OSM and sIL-6R, but not LIF and sgp130, a re useful indicators of CLL activity.