Effects of endogenous interleukin 1 on blast cells derived from acute myelogenous leukemia patients.
The in vitro effects of interleukin 1 (IL1) secreted by acute myelogenous leukemia (AML) blasts (termed endogenous IL 1 secretion) were investigated. Interleukin 1-dependent AML blast functions were inhibited during in vitro culture either by IL1-specific neutralizing antibodies (anti-IL1 alpha and anti-IL1 beta) or by the IL1 receptor antagonist (IL1RA). Endogenous IL1 secretion showed a wide variation between individual patients, but despite this variation IL1 inhibition significantly decreased both spontaneous blast proliferation and spontaneous blast secretion of IL1 alpha, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha and interleukin 6. In contrast to spontaneous blast proliferation, in the presence of exogenous hematopoietic growth factors (granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin 3, tumor necrosis factor alpha, stem cell factor), IL1 inhibition caused either increased or decreased AML blast proliferation depending on the individual patient. When AML blasts were cultured with stem cell factor plus granulocyte-macrophage colony-stimulating factor, IL1 inhibition significantly increased AML blast proliferation. Thus, IL1 is important for regulation of AML blast proliferation and cytokine secretion independent of the level of endogenous IL1 secretion, but the final effect of IL1 is highly dependent on the cytokine network in the AML blast microenvironment.
Bruserud
O
O
Medical Department B, Haukeland University Hospital, University of Bergen, Norway.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006041:Goats; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000502:physiology*; D007377:Interleukin-3 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012795:Sialoglycoproteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007377:Interleukin-3; D012795:Sialoglycoproteins; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor