Peripheral blood monocytes can be induced by stimuli such as bacterial lipopolysaccharide (LPS) to secrete an array of cytokines. We have studied the effects of interleukin 7 (IL-7) on human peripheral blood mononuclear cells (PBMC) and found that IL-7 is a relatively potent inducer of IL-6 secretion IL-6 protein levels were determined either by the B9 hybridoma growth factor assay or by enzyme-linked immunosorbent assay, and mRNA for IL-6 was analyzed by Northern hybridization. Detailed examination revealed that, among PBMC, monocytes, rather than lymphocytes, were secreting IL-6 in response to IL-7. In contrast to the low concentrations of IL-7 required to stimulate T cell growth and differentiation (as low as 0.1 ng/ml), relatively high concentrations of IL-7 were necessary to induce IL-6 secretion by monocytes (at least 10 ng/ml). An optimal concentration of IL-7 (100 ng/ml) induced monocytes to secrete 10-fold more IL-6 than an optimal concentration of IL-1 beta (10 ng/ml), and almost as much as LPS. However, significantly more IL-7 than IL-1 beta was required to induce detectable levels of IL-6. The kinetics of IL-6 secretion by monocytes were identical in response to IL-7, IL-1 beta, or LPS, with IL-6 protein detectable in culture supernatants as early as 2 h after the initiation of culture. IL-4 was found to markedly inhibit the ability of IL-7 or LPS to induce IL-6 mRNA and IL-6 secretion. In addition to promoting IL-6 production, IL-7 induced the secretion of immunoreactive IL-1 alpha, IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) by monocytes. IL-7 also induced monocyte/macrophage tumoricidal activity against a human melanoma cell target, an activity that may be related to the secretion of IL-1 alpha, IL-1 beta, and TNF-alpha. Finally, we used a whole blood culture system as a bridge to in vivo analysis to demonstrate that IL-7 induces cytokine secretion in the absence of culture medium, fetal calf serum, and adherence to plastic. Our data suggest that IL-7, in addition to regulating lymphocyte growth and differentiation, has potent effects on cells of the monocytic lineage. Thus, IL-7 may be an important mediator in inflammation and in the macrophage immune response to tumors.
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1 April 1991
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April 01 1991
Interleukin 7 induces cytokine secretion and tumoricidal activity by human peripheral blood monocytes.
M R Alderson,
M R Alderson
Department of Immunology, Immunex Corporation, Seattle, Washington 98101.
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T W Tough,
T W Tough
Department of Immunology, Immunex Corporation, Seattle, Washington 98101.
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S F Ziegler,
S F Ziegler
Department of Immunology, Immunex Corporation, Seattle, Washington 98101.
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K H Grabstein
K H Grabstein
Department of Immunology, Immunex Corporation, Seattle, Washington 98101.
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M R Alderson
Department of Immunology, Immunex Corporation, Seattle, Washington 98101.
T W Tough
Department of Immunology, Immunex Corporation, Seattle, Washington 98101.
S F Ziegler
Department of Immunology, Immunex Corporation, Seattle, Washington 98101.
K H Grabstein
Department of Immunology, Immunex Corporation, Seattle, Washington 98101.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1991) 173 (4): 923–930.
Citation
M R Alderson, T W Tough, S F Ziegler, K H Grabstein; Interleukin 7 induces cytokine secretion and tumoricidal activity by human peripheral blood monocytes.. J Exp Med 1 April 1991; 173 (4): 923–930. doi: https://doi.org/10.1084/jem.173.4.923
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