Interleukin-1 beta, interleukin-1 receptor antagonist and interleukin-6 plasma levels and cytokine gene polymorphisms in chronic lymphocytic leukemia: correlation with prognostic parameters

Background and Objectives. The growth of B-cell chronic lymphocytic leukemi a(B-CLL) cells has been shown to be dependent on exogenous growth factors i n vitro. We wanted to evaluate the clinical relevance of Interleukin (IL)-6 , Il-1 beta and interleukin-1 receptor antagonist (IL-1Ra) in B-CLL. As the plasma levels of IL-6, IL-1 beta and IL-1Ra have been suggested to be part ly dependent on gene polymorphism, the previously described polymorphisms o f the IL-1 complex genes and the IL-6 gene were also studied. Design and Methods. The plasma levels of these cytokines were measured in a cohort of 36 patients with B-CLL and in 400 healthy subjects. The previous ly described polymorphisms of the IL-1 complex genes and the IL-6 gene were studied using PCR and RFLP. These data was correlated with other parameter s associated with severity and prognosis of B-CLL and a number of clinical and laboratory findings. Results. The plasma concentrations of IL-1 beta and IL 1Ra-were lower in B- CLL patients than in normal controls (P < 0.001). The IL-1 beta plasma leve ls were dependent on the cell immunophenotype score and state of progressio n of the disease. Moreover, plasma concentrations of IL-6 were elevated in B-CLL patients compared with healthy subjects(p<0.005) correlated with dise ase stage, hemoglobin levels, anemia and erythrocyte sedimentation rate in the patients. The allele frequencies of the analyzed genes were similar in patients and controls. Interpretation and Conclusions. Our data demonstrate that in B-CLL, plasma levels of IL-1 beta, IL-1Ra and IL-6 differ from normal, and mechanisms oth er than, allelic imbalance of their genes account for the distinct cytokine profiles observed in this disease. (C) 2000, Ferrata Storti Foundation.