Divergent effects of IL-10 and IL-4 on the proliferation and growth factor secretion by acute myeloblastic leukemic cells.
The effects of interleukin-10 (IL-10) and IL-4 were studied on the spontaneous and IL-1, IL-3, and Granulocyte-Colony Stimulating Factor (G-CSF) supported proliferation of acute myeloid leukemic cells. IL-10 inhibited the spontaneous proliferation in 1 out of 12 (1/12) cases while the IL-1 stimulated the tritiated thymidine (3H-TdR) uptake was suppressed in 2/12 cases as a result of IL-10 administration. In the presence of G-CSF, IL-10 affected 3H-TdR uptake in 2/12 and no distinct changes were observed in the presence of IL-3. In contrast IL-4 alone stimulated (3H-TdR) uptake with a factor two or more in 7/12 cases. In the presence of IL-1 and G-CSF a further enhancement was noted in 2 and 5 cases respectively. In 2/12 cases IL-4 inhibited the spontaneous or IL-1 and G-CSF supported proliferation. To study whether the changes in 3H-TdR uptake are related to the endogenous secretion of G-CSF and GM-CSF, AML blast cells (n = 5) were cultured in medium supplemented with IL-1 or IL-3 in the absence and presence of IL-10 and IL-4. IL-10 did not inhibit the spontaneous secretion of G-CSF or GM-CSF but suppressed the IL-1 induced GM-CSF secretion in 2/5 cases. These moderate effects were observed despite the strong inhibition of IL-10 on the IL-6 secretion by human activated monocytes. In contrast to IL-10, IL-4 also inhibited the spontaneous (3/5) and cytokine induced (5/5) secretion of G-CSF and GM-CSF (4/5) protein in the cases in which an enhancement of the 3H-TdR uptake was noticed. In summary the data indicate that the proliferative effects of IL-4 are in some cases uncoupled from the endogenous secretion of cytokines. In addition IL-10 affects the AML cells in a limited number of cases despite the similarity in effects between IL-4 and IL-10 in suppressing cytokine secretion from activated human monocytes.
Tuyt
L M
LM
Department of Internal Medicine, University Hospital Groningen, Netherlands.
Dokter
W H
WH
Esselink
M T
MT
Vellenga
E
E
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000473:pathology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D006133:Growth Substances; D007377:Interleukin-3; D015850:Interleukin-6; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor