Faculty Collaboration Database

Suppression of chronic myelogenous leukemia colony growth by interleukin-4. Leukemia 1993 Feb;7(2):214-20

Date

02/01/1993

Pubmed ID

8426475

Scopus ID

2-s2.0-0027407487 (requires institutional sign-in at Scopus site)   18 Citations

Abstract

Interleukin-4 (IL-4) is a cytokine with pleiotropic activities. In normal bone marrow cultures grown in the presence of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), IL-4 suppresses granulocyte-macrophage colony-forming unit (CFU-GM) proliferation but it enhances the colony-stimulatory effect of granulocyte colony-stimulating factor (G-CSF). We studied the effect of IL-4 on chronic myelogenous leukemia (CML) bone marrow or peripheral blood cells from 30 patients using the CFU-granulocyte-erythrocyte-monocyte-megakaryocyte colony culture assay. In several repetitive experiments, IL-4 inhibited CFU-GM colony replication by 24 to 65% in a dose-dependent fashion at concentrations ranging from 0.01 to 10 micrograms/ml when patients' cells were cultured in the presence of erythropoietin alone or with phytohemagglutinin-conditioned medium, GM-CSF, or IL-3. The addition of 100 U/ml of IL-1 beta to the CML cultures partially reversed the inhibitory effect of IL-4. Incubation of CML low-density peripheral blood cells with IL-4 resulted in down-regulation of IL-1 beta and IL-6 production in three of four samples, suggesting that the suppressive effect of IL-4 is mediated by inhibition of IL-1 and by other mechanisms including inhibition of IL-6 production. In contrast to the stimulatory effect exerted by IL-4 on G-CSF-dependent CFU-GM progenitor proliferation in normal marrow, the addition of IL-4 to CML cultures grown in the presence of G-CSF resulted in a divergent effect: suppression of CML CFU-GM in two, stimulation in three, and no significant effect in two CML patients' samples. It is therefore possible that IL-4 may have an in vivo antiproliferative effect in a subpopulation of CML patients.

Author List

Estrov Z, Markowitz AB, Kurzrock R, Wetzler M, Kantarjian HM, Ferrajoli A, Gutterman JU, Talpaz M

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Colony-Forming Units Assay
Culture Media, Conditioned
Erythropoietin
Female
Granulocyte-Macrophage Colony-Stimulating Factor
Hematopoietic Stem Cells
Humans
Interleukin-1
Interleukin-4
Interleukin-6
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Male
Middle Aged
Phytohemagglutinins