Abstract
BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) exhibit elevated levels of various cytokines and increased numbers of immunosuppressive cell subpopulations. However, the relationship between cytokines and suppressor cells remains unclear. Studies in this field may contribute to a better understanding of the role of cytokines in the accumulation of suppressor cells. METHODS: Serum levels of 47 cytokines in patients with CLL and healthy donors were measured using multiplex analysis. The numbers of suppressor cells, including mMDSCs, Tregs, CD14+/IDO+ monocytes, and gMDSCs in peripheral blood, were determined using flow cytometry. RESULTS: A significant difference in the levels of 29 cytokines was observed between primary CLL patients and healthy donors. A statistically significant increase in the numbers of mMDSCs, Tregs, and CD14+/IDO+ monocytes was observed in CLL patients compared to healthy donors, while no significant differences were noted in the CD15+/LOX-1+gMDSCs numbers between CLL patients and healthy donors. Correlations were found between the levels of several cytokines and immunosuppressive cell numbers. Among these, two cytokines, MIP-1α and M-CSF, showed a positive correlation with two suppressor cell subpopulations. Furthermore, the levels of these cytokines differed between patients with Binet stage B and stage C CLL. CONCLUSIONS: Our findings suggest that these two cytokines play a key role in the immunosuppression observed in CLL patients. These results, demonstrating a correlation between cytokine levels and the numbers of suppressor cells in CLL patients, are consistent with our previous hypothesis. This hypothesis states that the simultaneous action of growth factors and pro-inflammatory cytokines can lead to immune system inhibition.