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-a (TNF -a), primarily monocyte-derived cytokines, form a group of proinflammatory cytokines with related and overlapping spectra of activities. The role of t hese cytokines in chronic myeloid leukemia (CML) has been investigated. A d istinctive pattern of cytokine secretion has been found in chronic myeloid leukemia in chronic phase (CML-CP), in blastic crisis (CML-BC) and in norma l subjects. Serum IL-6 levels in CML-CP and CML-BC were significantly raise d compared with normal controls (p=0.0026 for CML-CP and p=0.0011 for CML-B C). 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). I L-6 serum levels were found to correlate significantly with peripheral bloo d monocyte counts and bone marrow blast and basophil counts. We have analys ed monocyte/macrophage function with respect to their ability to produce IL -1, IL-6 and TNF-a, spontaneously as well as in response to LPS, in compari son with normal controls. A direct correlation of IL-6 levels in unstimulat ed and stimulated cultures with bone marrow blast and basophil counts has b een observed. From these results it is inferred that the monocyte function is impaired in CML patients, and the cytokine secretion is deficient. Our l imited data suggest that serum IL-6 levels may play an important role as a prognostic marker for CML. Copyright (C) 1998 John Wiley & Sons, Ltd.