Interleukin 10 inhibits cytokine production of human AML cells.
BACKGROUND
Unlike normal hematopoietic cells leukemic blasts from patients with AML constitutively express cytokines like IL1, GM-CSF and TNF alpha and it has been suggested that these cytokines may regulate growth and differentiation of the malignant cells. IL10 inhibits cytokine production of activated macrophages and T-helper 1 cells. We analysed whether IL10 can also suppress cytokine production and may inhibit growth of AML cells.


METHODS
AML blasts of 18 patients were purified by immunomagnetic separation and cultured in serum-free medium in the presence of cytokines. The production of cytokines was analysed by ELISA, DNA synthesis by 3H-thymidine incorporation and mRNA expression of cytokine genes by semiquantitative RT-PCR.


RESULTS
Our results confirm previous results that AML blasts produce a variety of cytokines such as GM-CSF, IL1 alpha, IL1 beta, IL6 and TNF alpha. AML cells were induced to proliferation by G-CSF, GM-CSF, IL3, IL1 beta and SCF to a different extent. In contrast, IL10 significantly inhibited the cytokine production at the mRNA and protein level and spontaneous thymidine uptake in a dose-dependent way. This inhibition could be abrogated by IL10 specific antibodies.


CONCLUSIONS
These observations suggest an inhibitory effect of IL10 on the proliferation of cultured AML blasts most likely through suppression of endogenous cytokines.
Westermann
F
F
Klinik I für Innere Medizin, Universität, Köln, Germany.
Kube
D
D
Haier
B
B
Bohlen
H
H
Engert
A
A
Zuehlsdorf
M
M
Diehl
V
V
Tesch
H
H
D000208:Acute Disease; D000368:Aged; D000911:Antibodies, Monoclonal; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000911:Antibodies, Monoclonal; D016207:Cytokines; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor