Relations between IL-3-induced proliferation and in vitro cytokine secretion of bone marrow cells from AML patients.
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.
Nowak
R
R
Medical Clinic I, Technical University of Dresden, Dresden, Germany.
Oelschlägel
U
U
Gurth
H
H
Range
U
U
Albrecht
S
S
Krebs
U
U
Hietschold
V
V
Ehninger
G
G
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000096:biosynthesis; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016014:Linear Models; D008875:Middle Aged; D015203:Reproducibility of Results; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007375:Interleukin-1; D007377:Interleukin-3; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha