Interleukin 1-dependent paracrine granulopoiesis in chronic granulocytic leukemia of the juvenile type

G. C. Bagby, C. A. Dinarello, R. C. Neerhout, D. Ridgway, E. McCall

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    Abstract

    Marrow and peripheral blood cells from nine children with juvenile chronic granulocytic leukemia (JCGL) demonstrated intense (94 ± 16% maximum) spontaneous granulocyte/macrophage colony growth but cells from five children with the adult variety of CGL did not. This unusual pattern of colony growth depended upon a stimulatory protein(s) produced by mononuclear phagocytes. No GM-CSA activity was found in any chromatofocused fraction of JCGL monocyte-conditioned media but an activity that induced GM-CSA in umbilical vein endothelial cells was detected at pI 6.9-7.2. Moreover, the CSA-inducing monokine was neutralized by an anti-IL-1 antibody in vitro and, in the one case so tested, the same antibody also inhibited 'spontaneous' colony growth. Therefore granulocyte/macrophage colony growth in JCGL is characteristically abnormal and distinguishes JCGL from the adult form of the disease. This abnormality depends upon the production, by mononuclear phagocytes, of IL-1 which, in turn, stimulates the release of high levels of colony stimulating activity by other cells. The high proliferative activity of CFU-GM we found in JCGL patients, and the high levels of GM-CSA found in their serum are compatible with the view that the in vitro abnormality reflects a similar abnormality in vivo.

    Original languageEnglish (US)
    Pages (from-to)1430-1436
    Number of pages7
    JournalJournal of Clinical Investigation
    Volume82
    Issue number4
    DOIs
    StatePublished - Jan 1 1988

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    ASJC Scopus subject areas

    • Medicine(all)

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