The cytokine interleukin (IL) 12 stimulates T cell and natural killer cell production of interferon (IFN) gamma and inhibits T cell production of IL-4. We investigated the effects of IL-12 on cytokine gene expression, immunoglobulin (Ig)E, mucosal mast cell, and eosinophil responses, and the course of infection in mice inoculated with the nematode parasite Nippostrongylus brasiliensis, as well as the IFN-gamma dependence of these effects. IL-12 stimulated IFN-gamma and IL-10 gene expression during primary and secondary N. brasiliensis infections and inhibited IL-3, IL-4, IL-5, and IL-9 gene expression during primary infections but had little inhibitory effect during secondary infections. IL-12 inhibited IgE, mucosal mast cell, and blood and tissue eosinophil responses during primary infections, but only eosinophil responses during secondary infections. IL-12 enhanced adult worm survival and egg production during primary, but not secondary infections. IL-12 needed to be administered by day 4 of a primary infection to inhibit IgE and mucosal mast cell responses, and by day 6 to strongly inhibit eosinophil responses and to enhance worm survival and fecundity. Anti-IFN-gamma mAb inhibited the effects of IL-12 on IgE secretion, intestinal mucosal mastocytosis, and parasite survival and fecundity, but did not affect IL-12 inhibition of eosinophilia. These observations indicate that IL-12, if administered during the initiation of eosinophilia. These observations indicate that IL-12, if administered during the initiation of an immune response, can change the response from one that is characterized by the production of T helper (Th)2-associated cytokines to one characterized by the production of Th-1 associated cytokines. However, IL-12 treatment has less of an effect once the production of Th2-associated cytokines has become established. In addition, our results provide evidence that Th2-associated responses protect against, and/or Th1-associated responses exacerbate, nematode infections.
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May 01 1994
Effects of interleukin 12 on immune responses and host protection in mice infected with intestinal nematode parasites.
F D Finkelman,
F D Finkelman
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
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K B Madden,
K B Madden
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
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A W Cheever,
A W Cheever
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
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I M Katona,
I M Katona
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
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S C Morris,
S C Morris
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
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M K Gately,
M K Gately
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
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B R Hubbard,
B R Hubbard
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
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W C Gause,
W C Gause
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
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J F Urban, Jr
J F Urban, Jr
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
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F D Finkelman
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
K B Madden
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
A W Cheever
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
I M Katona
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
S C Morris
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
M K Gately
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
B R Hubbard
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
W C Gause
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
J F Urban, Jr
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1994) 179 (5): 1563–1572.
Citation
F D Finkelman, K B Madden, A W Cheever, I M Katona, S C Morris, M K Gately, B R Hubbard, W C Gause, J F Urban; Effects of interleukin 12 on immune responses and host protection in mice infected with intestinal nematode parasites.. J Exp Med 1 May 1994; 179 (5): 1563–1572. doi: https://doi.org/10.1084/jem.179.5.1563
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