Relations between IL-3-induced proliferation and in vitro cytokine secretion of bone marrow cells from AML patients

Cytokine. 1999 Jun;11(6):435-42. doi: 10.1006/cyto.1998.0445.

Abstract

The influence of IL-3 on the bone marrow cells of 53 patients with acute myeloid leukaemia (AML) was investigated after 72 h suspension in cultures by analysing the proliferation of blasts and the secretion of cytokines. The titres of IL-1beta IL-6, TNF-alpha and IL-3 were measured in the supernatants of these cultures with ELISA tests. Comparing the percentage of cells in S-phases of control cultures and cultures with IL-3, the leukaemias were divided into two growth pattern groups: IL-3-insensitive (n=19) and IL-3-sensitive (n=34) leukaemias. The IL-3-insensitive AML cells show a greater ability for autonomous growth, first by the increase of S-phase in the control culture compared with the S-phase in vivo (P=0.0486) and second, by the higher constitutive secretion (control culture) of IL-1beta P =0.0004), IL-6 ( P =0.0395) and TNF-alpha P=0.0005). The IL-3-induced secondary cytokine secretion is also different in the two growth pattern groups. Whereas in the IL-3-insensitive AML cells a moderate increase of IL-1beta (1.48-fold increase) was present, in the IL-3-sensitive AML cells a 4.72-fold increase of IL-1beta 2.71-fold increase of IL-6 and 11.81-fold increase of the TNF-alpha titre could be detected. Overall, the data show an inverse correlation between the ability of AML cells to respond to IL-3 with increase of an S-phase and the constitutive secretion of IL-1beta, II-6 and TNF-alpha. A further effect of IL-3 is the induction of secondary cytokine secretion in the bone marrow of IL-3-sensitive growing AML cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / metabolism
  • Cell Division / drug effects
  • Cells, Cultured
  • Cytokines / metabolism*
  • Humans
  • Interleukin-1 / biosynthesis
  • Interleukin-3 / therapeutic use*
  • Interleukin-6 / biosynthesis
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / pathology
  • Leukemia, Myeloid / physiopathology
  • Linear Models
  • Middle Aged
  • Reproducibility of Results
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Cytokines
  • Interleukin-1
  • Interleukin-3
  • Interleukin-6
  • Tumor Necrosis Factor-alpha