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Interleukin-1 induces interleukin-6 production in peripheral blood
monocytes
G Tosato and KD Jones
Division of Biochemistry and Biophysics, Food and Drug Administration,
Bethesda, MD.
Interleukin-6 (IL-6), a multifunctional cytokine produced in monocytes,
fibroblasts, endothelial cells, and keratinocytes, is induced by a variety
of stimulating signals, including lipopolysaccharide (LPS), poly (I), poly
(C), IL-1, tumor necrosis factor (TNF), and platelet- derived growth
factor. Some of these signals induce IL-6 effectively only in one cell
type, and this selectivity of induction may explain selectivity of biologic
effects. In the present study, we show that IL- 1 beta, previously known to
be a potent inducer of IL-6 in fibroblasts, endothelial cells, and
keratinocytes, but not in monocytes, is also a potent inducer of IL-6 in
peripheral blood monocytes. High level IL-6 activity that could be
neutralized by specific antibodies to IL-6 was detected in supernatants of
IL-1-stimulated monocytes. Maximal induction required IL-1 concentrations
of 10 ng/mL. As judged by sodium dodecyl sulfate-polyacrylamide gel
electrophoresis under reducing conditions, IL-6 species of relative
molecular mass of 19 to 26 Kd could be specifically immunoprecipitated from
supernatants of IL-1- induced monocytes. Size heterogeneity is a reported
feature of IL-6 produced in a variety of cell types, and monocyte-derived
IL-6 induced by either IL-1 or LPS displayed similar size heterogeneity.
The highly purified recombinant IL-1 beta preparation used contained
little, if any, LPS. In addition, monocyte production of IL-6, induced by
IL-1 beta, was specifically neutralized by anti-IL-1 beta antibodies,
demonstrating that IL-1, rather than a contaminant in the IL-1 preparation,
was responsible for IL-6 induction. A number of biologic activities have
been ascribed both to IL-1 and IL-6. The finding that IL-1 induced IL-6 in
monocytes may help in defining the spectrum of biologic activities of each
of these interactive cytokines.
Volume 75,
Issue 6,
pp. 1305-1310,
03/15/1990
Copyright © 1990 by The American Society of Hematology
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