Neutralization of IL-12 decreases resistance to Listeria in SCID and C.B- 17 mice: Reversal by IFN-γ

C. S. Tripp, M. K. Gately, J. Hakimi, P. Ling, E. R. Unanue

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307 Scopus citations

Abstract

Interleukin-12 (IL-12) is necessary for the production of IFN-γ by NK cells during the generation of innate immunity and by T cells for the development of the Th1 response during specific cell mediated immunity. Here we demonstrate that the endogenous production of IL-12 is critical to the survival of both immunocompromised SCID mice and normal C.B-17 control mice during a primary infection with Listeria monocytogenes. When IL-12 is neutralized in vivo, both strains of mice die at a normally sublethal dose of Listeria. Anti-IL-12 antibody-treated mice showed a decrease in macrophage I- A(d) expression and an increased Listeria burden in the spleen. Furthermore, as has been demonstrated in vitro, these effects of IL-12 in vivo were predominantly regulated through the production of IFN-γ. Administration of IFN-γ simultaneously with neutralizing antibodies to IL-12 restored macrophage I-A(d) expression, limited the spread of the infection, and resulted in the survival of SCID mice. Thus, IL-12 is critical for resistance to infection with Listeria monocytogenes, and this resistance is mediated through stimulation by IL-12 of IFN-γ production. Concomitant experiments confirmed that anti-TNF antibodies also resulted in uncontrolled infection and a decrease in macrophage I-A(d) expression. However, administration of IFN-γ restored the levels of I-A(d) in macrophages but did not limit Listeria growth.

Original languageEnglish
Pages (from-to)1883-1887
Number of pages5
JournalJournal of Immunology
Volume152
Issue number4
StatePublished - Jan 1 1994

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