The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/6/2103/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 12, June 15, 1998 2103-2108

Brief Definitive Reports

Murine Macrophages Secrete Interferon {gamma} upon Combined Stimulation with Interleukin (IL)-12 and IL-18: A Novel Pathway of Autocrine Macrophage Activation

Markus Munder, Moisés Mallo, Klaus Eichmann, and Manuel Modolell

From the Max-Planck-Institut für Immunbiologie, D-79108 Freiburg, Germany

Interferon (IFN)-{gamma}, a key immunoregulatory cytokine, has been thought to be produced solely by activated T cells and natural killer cells. In this study, we show that murine bone marrow– derived macrophages (BMM{Phi}) secrete large amounts of IFN-{gamma} upon appropriate stimulation. Although interleukin (IL)-12 and IL-18 alone induce low levels of IFN-{gamma} mRNA transcripts, the combined stimulation of BMM{Phi} with both cytokines leads to the efficient production of IFN-{gamma} protein. The macrophage-derived IFN-{gamma} is biologically active as shown by induction of inducible nitric oxide synthase as well as upregulation of CD40 in macrophages. Our findings uncover a novel pathway of autocrine macrophage activation by demonstrating that the macrophage is not only a key cell type responding to IFN-{gamma} but also a potent IFN-{gamma}–producing cell.

Key Words: macrophage • interferon {gamma} • interleukin 12 • interleukin 18 • innate immunity

Address correspondence to Manuel Modolell, Max-Planck-Institut für Immunbiologie, Stübeweg 51, D-79108 Freiburg, Germany. Phone: 49-761-5108-535; Fax: 49-761-5108-534; E-mail: modolell{at}immunbio.mpg.de


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