Abnormal levels of proinflammatory cytokines in serum and monocyte cultures from patients with chronic myeloid leukemia in different stages, and their role in prognosis.

Interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), primarily monocyte-derived cytokines, form a group of proinflammatory cytokines with related and overlapping spectra of activities. The role of these cytokines in chronic myeloid leukemia (CML) has been investigated. A distinctive pattern of cytokine secretion has been found in chronic myeloid leukemia in chronic phase (CML-CP), in blastic crisis (CML-BC) and in normal subjects. Serum IL-6 levels in CML-CP and CML-BC were significantly raised compared with normal controls (p = 0.0026 for CML-CP and p = 0.0011 for CML-BC). IL-6 was significantly elevated in blastic crisis of CML (103.5 +/- 20.77 pg ml-1) compared with CML-CP (37.35 +/- 10.88 pg ml-1; p = 0.014). IL-6 serum levels were found to correlate significantly with peripheral blood monocyte counts and bone marrow blast and basophil counts. We have analysed monocyte/macrophage function with respect to their ability to produce IL-1, IL-6 and TNF-alpha, spontaneously as well as in response to LPS, in comparison with normal controls. A direct correlation of IL-6 levels in unstimulated and stimulated cultures with bone marrow blast and basophil counts has been observed. From these results it is inferred that the monocyte function is impaired in CML patients, and the cytokine secretion is deficient. Our limited data suggest that serum IL-6 levels may play an important role as a prognostic marker for CML.