Faculty Collaboration Database

Suppression of chronic myelogenous leukemia colony growth by interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptors: a novel application for inhibitors of IL-1 activity. Blood 1991 Sep 15;78(6):1476-84

Date

09/15/1991

Pubmed ID

1715791

Scopus ID

2-s2.0-0025946285 (requires institutional sign-in at Scopus site)   92 Citations

Abstract

In this study, we investigated the role of interleukin-1 beta (IL-1 beta) in the malignant evolution of chronic myelogenous leukemia (CML) and the functional activity of IL-1 inhibitors. Bone marrow (BM) and peripheral blood (PB) low-density cells from 38 CML patients were studied in the colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte colony culture assay. Samples from patients with early stage, interferon-alpha (IFN)-sensitive disease formed hematopoietic colonies in the presence of fetal calf serum (FCS), erythropoietin (Epo), and one of the following: granulocyte-macrophage colony-stimulating factor (10 ng/mL), IL-3 (15 ng/mL), both, or phytohemagglutinin-conditioned medium. The addition of IL-1 beta augmented IFN-sensitive CML colony growth in a dose-dependent manner at concentrations of 10 to 100 U/mL. In sharp contrast, addition of the above growth factors did not augment the colony growth-promoting effect of FCS and Epo in samples from IFN-resistant patients; further, adherent cell fractionation or T-lymphocyte depletion attenuated the "autonomous" colony growth. Lysates of 2.5 x 10(7) low-density cells from each of six IFN-resistant and six IFN-sensitive CML patients and three normal volunteers were tested for intrinsic IL-1 beta content in an enzyme-linked immunosorbent assay and yielded a mean of 610 pg, 54.6 pg, and 49.4 pg of IL-1 beta, respectively (P less than .045). Interestingly, both soluble IL-1 receptors (sIL-1R) and IL-1 receptor antagonist (IL-1RA) at concentrations of 5 to 100 ng/mL (sIL-1R) and 10 to 500 ng/mL (IL-1RA) inhibited CML colony growth in a dose-dependent fashion, with maximal inhibition of 64% and 65%, respectively. A similar effect was noted with the use of anti-IL-1 beta neutralizing antibodies. These data implicate IL-1 beta in CML disease progression and suggest that the inhibitory effects of molecules such as sIL-1R and IL-1RA could conceivably be the basis of a novel therapeutic strategy against this disorder.

Author List

Estrov Z, Kurzrock R, Wetzler M, Kantarjian H, Blake M, Harris D, 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

Adolescent
Adult
Aged
Drug Resistance
Female
Granulocyte-Macrophage Colony-Stimulating Factor
Humans
Interferons
Interleukin 1 Receptor Antagonist Protein
Interleukin-1
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Male
Middle Aged
Proteins
Receptors, Immunologic
Receptors, Interleukin-1
Sialoglycoproteins
Tumor Stem Cell Assay